Cancer Research and Treatment

Original Articles

Platinum and 5-Fluorouracil Salvage Therapy for Severe Liver Crisis in Metastatic Breast Cancer: Efficacy and Analysis of Prognostic Factors: I-Wei Ho, Jiun-I Lai, Chun-Yu Liu, Wei-Chi Lin, Muh-Hwa Yang, Ling-Ming Tseng, Ta-Chung Chao; Received November 18, 2025 Accepted December 28, 2025 Published online December 29, 2025; DOI: https://doi.org/10.4143/crt.2025.1262 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Metastatic breast cancer (MBC) with severe hepatic dysfunction due to liver crisis presents a significant treatment challenge, as conventional chemotherapy often requires dose modifications, leading to reduced efficacy. The combination of platinum, 5-fluorouracil, and folinate (PFL) offers a rational treatment strategy. This study evaluates the efficacy and safety of PFL in MBC patients with liver crisis and explores predictive markers for treatment response.
Materials and Methods
This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, included 44 MBC patients with bilirubin ≥ 3 mg/dL treated between January 2015 and June 2024. Outcomes included bilirubin response rate (≥ 50% reduction from baseline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. The area under the curve analysis was used to determine the optimal cutoff for liver function assessment models, and Cox regression identified independent prognostic factors.
Results
Among the 44 patients, 47.7% achieved a bilirubin response within a median of 19 days. Overall, the median PFS and OS were 1.4 and 1.9 months, respectively, but improved to 4.6 and 7.8 months in those achieving bilirubin response. The objective response rate was 22.7%, and the disease control rate was 29.5%. A fibrosis-4 (FIB-4) score < 9.1 predicted a 65% bilirubin response rate, while FIB-4 > 9.1 was also an independent predictor of OS. Grade 3 adverse events occurred in 36.4% of patients.
Conclusion
The PFL regimen is effective in MBC patients with severe liver crisis with hyperbilirubinemia. A FIB-4 score < 9.1 may serve as a potential prognostic factor for bilirubin response and is associated with improved survival outcomes.

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Immunosuppressive Tumor Microenvironment in Colorectal Cancer Lung Metastases: Implications for Recurrence after Metastasectomy: Minsuk Kwon, Min-Kyue Shin, Minae An, Yeong Jeong Jeon, Tae Hee Hong, Jung Kyong Shin, Sung Hee Lim, Yoonah Park, Yong Beom Cho, Seung Tae Kim, Yong Soo Choi, Jeeyun Lee; Received July 3, 2025 Accepted December 8, 2025 Published online December 17, 2025; DOI: https://doi.org/10.4143/crt.2025.691 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.
Materials and Methods
Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.
Results
Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T-cell activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.
Conclusion
Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

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Obesity promotes aggressiveness of endometrial cancer via metabolic reprogramming and intercellular crosstalk in the tumor microenvironment
Yu Chen, Yijin Fang, Guozhi Zhao, Yuanqun Zhou, Dong-Hua Yang, Jian Han, Ying Zheng
Cancer Letters.2026; 656: 218649. CrossRef

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Hematologic malignancy

Clinicopathological Significance of Tumor-Infiltrating T Lymphocytes and Macrophages in Primary Large B-Cell Lymphoma of Immune-Privileged Sites: Jinseong Kim, Deokhoon Kim, Hyungwoo Cho, Dok Hyun Yoon, Heounjeong Go; Cancer Res Treat. 2026;58(3):931-944. Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.641

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immune-privileged large B-cell lymphomas (IP-LBCLs), comprising primary central nervous system lymphoma (PCNS-LBCL), primary vitreoretinal lymphoma (PVR-LBCL), and primary testicular lymphoma (PT-LBCL), originate in sites with limited immune surveillance. Owing to their rarity, the prognostic implications of the tumor microenvironment in IP-LBCLs remain unclear, warranting further investigation.
Materials and Methods
This study evaluated 109 IP-LBCL cases (PCNS-LBCL, n=87; PT-LBCL, n=22; six cases of PVR-LBCL excluded) using multiplex immunohistochemistry on tissue microarrays, along with clinicopathological analysis. Immune cell infiltration, tumor major histocompatibility complex (MHC) class I, and programmed death ligand-1 (PD-L1) expression, and their associations with clinical outcomes, were evaluated.
Results
PT-LBCL demonstrated higher infiltration of all tumor-infiltrating T lymphocyte (TIL) subsets than PCNS-LBCL (all p < 0.05). Elevated CD4⁺ and CD8⁺ T-cell levels correlated with prolonged progression-free survival (PFS) (both p < 0.05). M1 macrophage infiltration was associated with improved PFS (p=0.005) and independently predicted a favorable prognosis (hazard ratio, 0.49; p=0.041). Loss of MHC class I expression was more frequent in PT-LBCL than in PCNS-LBCL (77.3% vs. 9.2%, p < 0.001). TIL infiltration predicted improved PFS only when the tumor MHC class I was preserved. Moreover, programmed death protein-1 (PD-1)⁺ TILs and tumor PD-L1 expression were associated with prognosis in conjunction with various clinicopathological variables.
Conclusion
These findings highlight the favorable prognostic role of TILs and M1 macrophages, and underscore the complex immune–tumor interactions in IP-LBCLs, despite their origin in immune-privileged sites.

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The Landscape of Primary Central Nervous System Lymphoma (PCNSL): Clinicopathologic and Genomic Characteristics and Therapeutic Perspectives
Huijuan Jiang, Lin Nong
Cancers.2025; 17(17): 2909. CrossRef

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Gastrointestinal cancer

Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers: Hyun Gu Lee, Yeseul Kim, Mi-Ju Kim, Yeon Wook Kim, Sun-Young Jun, Deokhoon Kim, In Ja Park, Seung-Mo Hong; Cancer Res Treat. 2026;58(1):264-274. Published online February 18, 2025; DOI: https://doi.org/10.4143/crt.2024.947

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Purpose
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
Materials and Methods
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor.
Results
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
Conclusion
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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Synchronous multiple primary colorectal cancer with discordant RAS status between primary lesions: a case report in an elderly patient
Junting Guan, Jiyuan Chen, Shengqi Pan, Qi Li, Guiyu Wang, Qingchao Tang
Frontiers in Surgery.2026;[Epub] CrossRef

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Breast cancer

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions: Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes; Cancer Res Treat. 2024;56(1):178-190. Published online August 1, 2023; DOI: https://doi.org/10.4143/crt.2023.386

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Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

Citations

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Prognostic Impact of Real-World Immunohistochemical Changes in Breast Cancer Treated with Neoadjuvant Chemotherapy
Marcelo Antonini, André Mattar, Marcelo Madeira, Letícia Xavier Félix, Julio Antonio Pereira de Araújo, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antonio Luis Frasson, Eduardo Camargo Millen, Marina Diógenes Teixeira, Lariss
Clinical Breast Cancer.2026; 26(1): 276. CrossRef
Immunohistochemical Changes After Neoadjuvant Chemotherapy and Their Impact on Breast Cancer Survival: A Systematic Review and Meta-analysis
Marcelo Antonini, André Mattar, Gil Facina, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antônio Luis Frasson, Eduardo Camargo Millen, Rodrigo Caires Campos, Letícia Xavier Félix, Juliana Calado Vieira, Marina Diógenes Teixeira
Clinical Breast Cancer.2026; 26(3): 208. CrossRef
Prognostic value of prognostic nutritional index in breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis
Meihui Shan, Ziqian Zhao, Munawar Anwar, Jiawei Chen, Yuquan Dai, Yeliya Yeerboli, Zuqiang Xu, Zizhang Wang, Le Yang, Chao Dong
Frontiers in Oncology.2026;[Epub] CrossRef
Discordance in Immunohistochemistry Results in Breast Pathologies: Effect of Chemotherapy, Specimen Characteristics, or Pathology Center?
Mustafa Ersoy
Clinical Medicine Insights: Oncology.2025;[Epub] CrossRef
Identifying gene expression signatures of oncolytic virus response in patient-derived pancreatic ductal adenocarcinoma organoids
Marco Huberts, Elham Aida Farshadi, Farzana Mohammad, Jie Ju, Andrew Stubbs, Ron A.M. Fouchier, Bernadette G. van den Hoogen
Molecular Therapy Oncology.2025; 33(4): 201064. CrossRef
Post-Surgical Reassessment of Breast Cancer IHC: Concordance, Δ-Metrics, and Treatment-Relevant Reclassification
Ramona Andreea Cioroianu, Michael Schenker, Tradian Ciprian Berisha, Virginia-Maria Rădulescu, George Ovidiu Cioroianu, Raluca Chirculescu, Ana Maria Petrescu, Mihaela Popescu, Anda Lorena Dijmărescu, Stelian Ștefăniță Mogoantă
Diagnostics.2025; 15(24): 3128. CrossRef

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The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer: In Hye Song, Young-Ae Kim, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, Yeon ho Choi, Heejae Lee, Jeong-Han Seo, Youngjin Cho, Sung Wook Jung, Hee Jeong Kim, Sei Hyun Ahn, Hee Jin Lee, Gyungyub Gong; Cancer Res Treat. 2022;54(4):1111-1120. Published online December 21, 2021; DOI: https://doi.org/10.4143/crt.2021.1017

Abstract PDF Supplementary Material PubReader ePub

Purpose
The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.
Materials and Methods
The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.
Results
HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.
Conclusion
MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

Citations

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The Immunoregulatory Roles of ERα in Breast Cancer: Mechanisms, Crosstalk, and Therapeutic Insights
Afsoon Dehghani
Journal of Cancer Prevention.2026; 31(1): 1. CrossRef
Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis
Bernard Friedenson
JMIRx Med.2025; 6: e50712. CrossRef
Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer
Julio C Tinoco, Harmony I Saunders, Lauryn Rose Werner, Xiaopeng Sun, Eilidh I Chowanec, Amanda Heard, Prabhakar Chalise, Jeffery M Vahrenkamp, Andrea E Wilson, Cong-Xiao Liu, Gangjun Lei, Junping Wei, Hugo Cros, Hisham Mohammed, Melissa Troester, Charles
Journal for ImmunoTherapy of Cancer.2025; 13(3): e010179. CrossRef
Neoadjuvant Chemotherapy Efficacy in Breast Cancer: Insights from Magnetic Resonance Imaging Compilation (MAGIC)
Honghong Wu, Zebo Huang, Jie Wang
Academic Radiology.2025; 32(8): 4369. CrossRef
Prenatal Bisphenol B Exposure Induces Adult Male Offspring Reproductive Dysfunction via ERα Inhibition-Triggered MHC I-Mediated Testicular Immunological Responses
Nannan Chen, Xiaotian Li, Shenrui Zhou, Xin Peng, Senlin Xue, Yuetong Liu, Tingwang Jiang, Wei Yan
Toxics.2025; 13(6): 423. CrossRef
The untapped potential of radiation and immunotherapy for hormone receptor-positive breast cancer
Matthew Fenton, Miki Yoneyama, Erik Wennerberg, Tom Lund, Andrew Tutt, Alan Melcher, Sandra Demaria, Navita Somaiah
npj Breast Cancer.2025;[Epub] CrossRef
Dendrimer-Mediated Delivery Enhances Therapeutic Efficacy in Triple-Negative Breast Cancer
Anunay James Pulukuri, Anubhav Dhull, Aqib Iqbal Dar, Anu Rani, Rishi Sharma, Clifford E. Berkman, Anjali Sharma
Biomacromolecules.2025; 26(9): 5979. CrossRef
Neoadjuvant Immunotherapy in Hormone Receptor-Positive Breast Cancer: From Tumor Microenvironment Reprogramming to Combination Therapy Strategies
Zimei Tang, Tao Huang, Tinglin Yang
International Journal of Molecular Sciences.2025; 26(23): 11596. CrossRef
Toxic Epidermal Necrolysis and Steven–Johnson Syndrome During the Postpartum Period: A Literature Review with a Rare Case Presentation
Natalia Katarzyna Mazur-Ejankowska, Maciej Ejankowski, Magdalena Emilia Grzybowska, Jakub Żółkiewicz, Ewa Gostkowska, Wioletta Barańska-Rybak, Dariusz Grzegorz Wydra
Journal of Clinical Medicine.2025; 15(1): 17. CrossRef
Estrogen receptor regulation of the immune microenvironment in breast cancer
Conor McGuinness, Kara L. Britt
The Journal of Steroid Biochemistry and Molecular Biology.2024; 240: 106517. CrossRef
Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer
Xin Li, Zilun Ruan, Shuzhen Yang, Qing Yang, Jinpeng Li, Mingming Hu
International Journal of Molecular Sciences.2024; 25(19): 10546. CrossRef
Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity
Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, Nicolas Larmonier
International Journal of Molecular Sciences.2023; 24(20): 15048. CrossRef

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Lung and Thoracic cancer

The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non–Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors: Xiaoyan Sun, Yingnan Feng, Bin Zhang, Wuhao Huang, Xiaoliang Zhao, Hua Zhang, Dongsheng Yue, Changli Wang; Cancer Res Treat. 2022;54(4):1017-1029. Published online November 23, 2021; DOI: https://doi.org/10.4143/crt.2021.1007

Abstract PDF PubReader ePub

Purpose
The aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC).
Materials and Methods
Resectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery.
Results
A total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group.
Conclusion
High NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

Citations

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Pathologic assessment of resected stage III non‐small cell lung cancer after neoadjuvant chemotherapy: identification of additional prognostic factors
Francesca Lunardi, Alessandra Ferro, Luca Vedovelli, Federica Pezzuto, Sofia‐Eleni Tzorakoleftheraki, Asuman Kilitci, Yuliia Kuzyk, Simone Zanella, Marco Schiavon, Federico Rea, Giulia Pasello, Fiorella Calabrese
Histopathology.2026; 88(3): 710. CrossRef
Intratumoral and peritumoral heterogeneity based on CT to predict the pathological response after neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma
Xiaodong Ling, Xiaolong Yang, Ping Wang, Yingjie Li, Zhubin Wen, Jiayang Wang, Kaige Chen, Yanhong Yu, Aoyu Liu, Jianqun Ma, Wei Meng
International Journal of Surgery.2026; 112(1): 314. CrossRef
Evaluation of inflammatory parameters and ferritin as prognostic factors in non-small cell lung cancer patients receiving nivolumab immunotherapy
İsmail Beypınar, Onur Yazdan Balçık, Semiha Urvay, Müslih Ürün, Berrak Erçek, Hacer Demir, Canan Yıldız, Murat Araz, Ahmet Oruç, Yusuf İlhan, Utku Özilice, Aziz Kurtulus
Biomarkers.2026; 31(2): 91. CrossRef
Construction of a prognosis forecasting model for immuno-therapy response in cancer patients by integrating routine clinical parameters and tumor mutational burden
Xudong ZHU, Shuqiang HAO, Zhen CHENG, Weijia FANG
Journal of Zhejiang University (Medical Sciences).2026; 55(1): 36. CrossRef
Perioperative inflammatory index differences between pulmonary squamous cell carcinoma and adenocarcinoma and their prognostic implications
Yi Liu, Songping Cui, Jing Wang, Bin Hu, Shuo Chen
Frontiers in Oncology.2025;[Epub] CrossRef
Predictive factors of treatment efficacy and prognosis in patients with resectable non–small cell lung cancer following neoadjuvant chemoimmunotherapy
Zhaoxin Chen, Zhendong Lu, Mengdong Zhang, Dan Zhao, Wei Li, Siyun Fu, Liang Shi, Junfang Tang, Zhe Liu, Jinghui Wang, Dongpo Wang
Oncology and Translational Medicine.2025; 11(5): 221. CrossRef
Carcinoembryonic antigen as a predictor of treatment outcomes in cancer patients receiving immune checkpoint inhibitors
Wangbin Ma, Qiao Shi, Xiaozhe Su, Lilong Zhang, Chen Chen, Chao Zhang, Ying Wang
Annals of Medicine.2025;[Epub] CrossRef
The Value of Dynamic of Alkaline Phosphatase and Neutrophil-to-Lymphocyte Ratio in Predicting the Efficacy of Neoadjuvant Immunochemotherapy in Patients with Non-Small Cell Lung Cancer
Li Gong, Qihang Yan, Dachuan Liang, Liang Li, Jie Yang, Wingshing Wong, Shuyue Zhang, Shuqin Dai, Wenyu Zhai, Junye Wang
Journal of Inflammation Research.2025; Volume 18: 14827. CrossRef
Circulating biomarkers as predictors of response to immune checkpoint inhibitors in NSCLC: Are we on the right path?
Calogera Claudia Spagnolo, Francesco Pepe, Giuliana Ciappina, Francesco Nucera, Paolo Ruggeri, Andrea Squeri, Desirèe Speranza, Nicola Silvestris, Umberto Malapelle, Mariacarmela Santarpia
Critical Reviews in Oncology/Hematology.2024; 197: 104332. CrossRef
Easily applicable predictive score for MPR based on parameters before neoadjuvant chemoimmunotherapy in operable NSCLC: a single-center, ambispective, observational study
Mingming Hu, Xiaomi Li, Haifeng Lin, Baohua Lu, Qunhui Wang, Li Tong, Hongxia Li, Nanying Che, Shaojun Hung, Yi Han, Kang Shi, Chenghai Li, Hongmei Zhang, Zhidong Liu, Tongmei Zhang
International Journal of Surgery.2024; 110(4): 2275. CrossRef
Dynamics of peripheral blood inflammatory index predict tumor pathological response and survival among patients with locally advanced non-small cell lung cancer who underwent neoadjuvant immunochemotherapy: a multi-cohort retrospective study
Wenyu Zhai, Chao Zhang, Fangfang Duan, Jingdun Xie, Shuqin Dai, Yaobin Lin, Qihang Yan, Bingyu Rao, Liang Li, Yuheng Zhou, Zerui Zhao, Hao Long, Junye Wang
Frontiers in Immunology.2024;[Epub] CrossRef
Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology
Xiao Zhang, Zhenyu Lin, Yuan Feng, Zhaoguo Lin, Kaixiong Tao, Tao Zhang, Xiaoli Lan
Journal of Nuclear Medicine.2024; 65(10): 1548. CrossRef
Radiomics nomogram combined with clinical factors for predicting pathological complete response in resectable esophageal squamous cell carcinoma
Zihao Lu, Yongsen Li, Wenxuan Hu, Yonghao Cao, Xin Lv, Xinyu Jia, Shiyu Shen, Jun Zhao, Chun Xu
Frontiers in Oncology.2024;[Epub] CrossRef
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Zhao Shuang, Xiong Xingyu, Cheng Yue, Yu Mingjing
The Clinical Respiratory Journal.2024;[Epub] CrossRef
Mean platelet volume/platelet count ratio in combination with tumor markers in colorectal cancer: a retrospective clinical study
Huan Zhang, Fan Lin, Zhuocai Wang
BMC Cancer.2023;[Epub] CrossRef
Development and validation of a radiomics-based nomogram for predicting a major pathological response to neoadjuvant immunochemotherapy for patients with potentially resectable non-small cell lung cancer
Chaoyuan Liu, Wei Zhao, Junpeng Xie, Huashan Lin, Xingsheng Hu, Chang Li, Youlan Shang, Yapeng Wang, Yingjia Jiang, Mengge Ding, Muyun Peng, Tian Xu, Ao’ran Hu, Yuda Huang, Yuan Gao, Xianling Liu, Jun Liu, Fang Ma
Frontiers in Immunology.2023;[Epub] CrossRef
Prognostic role of preoperative inflammatory markers in postoperative patients with colorectal cancer
Zilong Xiao, Xinxin Wang, Xiaoxiao Chen, Jiawei Zhou, Haitao Zhu, Jiangnan Zhang, Wensheng Deng
Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy
Wen-Yu Zhai, Fang-Fang Duan, Yao-Bin Lin, Yong-Bin Lin, Ze-Rui Zhao, Jun-Ye Wang, Bing-Yu Rao, Lie Zheng, Hao Long
Journal of Inflammation Research.2023; Volume 16: 3329. CrossRef
The predictive value of 18F-FDG PET/CT combined with inflammatory index for major pathological reactions in resectable NSCLC receiving neoadjuvant immunochemotherapy
Xiaoqin Yin, Jian Li, Bei Chen, Kehuang Liu, Shuo Hu
Lung Cancer.2023; 186: 107389. CrossRef
Efficacy, safety, and survival of neoadjuvant immunochemotherapy in operable non-small cell lung cancer: a systematic review and meta-analysis
Yue Zheng, Baijie Feng, Jingyao Chen, Liting You
Frontiers in Immunology.2023;[Epub] CrossRef
Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC
Ana Oitabén, Pablo Fonseca, María J. Villanueva, Carme García-Benito, Aida López-López, Alberto Garrido-Fernández, Clara González-Ojea, Laura Juaneda-Magdalena, Martín E. Lázaro, Mónica Martínez-Fernández
Cancers.2022; 14(11): 2626. CrossRef

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Pediatric cancer

Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors: Gyu Sang Yoo, Jeong Il Yu, Sungkoo Cho, Youngyih Han, Yoonjin Oh, Do Hoon Lim, Hee Rim Nam, Ji-Won Lee, Ki-Woong Sung, Hyung Jin Shin; Cancer Res Treat. 2022;54(3):907-916. Published online October 15, 2021; DOI: https://doi.org/10.4143/crt.2021.332

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors.
Materials and Methods
We retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHb_avg), absolute lymphocyte counts (ΔALC_avg), and platelet counts (ΔPLT_avg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3-4 weeks after the completion of radiotherapy using t test and mixed-model analysis.
Results
The PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHb_avg between the two groups at any timepoint. However, ΔALC_avg and ΔPLT_avg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group.
Conclusion
PrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.

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General

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort: Hwa Kyung Byun, Seung Yeun Chung, Kyoung-Jin Kim, Jinsil Seong; Cancer Res Treat. 2021;53(4):962-972. Published online January 26, 2021; DOI: https://doi.org/10.4143/crt.2020.1053

Abstract PDF Supplementary Material PubReader ePub

Purpose
Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.
Materials and Methods
A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.
Results
Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.
Conclusion
IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

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Gastrointestinal Cancer

LASSO-Based Machine Learning Algorithm for Prediction of Lymph Node Metastasis in T1 Colorectal Cancer: Jeonghyun Kang, Yoon Jung Choi, Im-kyung Kim, Hye Sun Lee, Hogeun Kim, Seung Hyuk Baik, Nam Kyu Kim, Kang Young Lee; Cancer Res Treat. 2021;53(3):773-783. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.974

Abstract PDF Supplementary Material PubReader ePub

Purpose
The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning–based approach has not been widely studied.
Materials and Methods
Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set.
Results
LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model.
Conclusion
Our LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.

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European Journal of Medical Research.2025;[Epub] CrossRef
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Significant adverse prognostic events in patients with urosepsis: a machine learning based model development and validation study
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Dendrobin A inhibits gastric cancer: Mechanistic insights supported by integrated evidence
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Machine Learning Integration of Bulk and Single-Cell RNA-Seq Data Reveals Cathepsin B as a Central PANoptosis Regulator in Influenza
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Prediction Models of Microinvasive Cervical Cancer in High-Grade Squamous Intraepithelial Lesion Treatment by Loop Electrosurgical Excision Procedure
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Interpretable Machine Learning Models for Predicting Lateral Pelvic Lymph Node Metastasis in Rectal Cancer: A Chinese Multicenter Retrospective Study
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T Cells Modified with CD70 as an Alternative Cellular Vaccine for Antitumor Immunity: Sang-Eun Lee, A-Ri Shin, Hyun-Jung Sohn, Hyun-Il Cho, Tai-Gyu Kim; Cancer Res Treat. 2020;52(3):747-763. Published online February 14, 2020; DOI: https://doi.org/10.4143/crt.2019.721

Abstract PDF PubReader ePub

Purpose
Successful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen-presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell–based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals.
Materials and Methods
Antigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax).
Results
T cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization.
Conclusion
These results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.

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Kai Shen, Tong Liu
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294 Download
5 Web of Science
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Changes of Tumor Infiltrating Lymphocytes after Core Needle Biopsy and the Prognostic Implications in Early Stage Breast Cancer: A Retrospective Study: Jiahui Huang, Xiaosong Chen, Xiaochun Fei, Ou Huang, Jiayi Wu, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Kunwei Shen; Cancer Res Treat. 2019;51(4):1336-1346. Published online February 12, 2019; DOI: https://doi.org/10.4143/crt.2018.504

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes.
Materials and Methods
A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with ≥50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival.
Results
SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p<0.001). Younger age (<60 years, p=0.016) and long surgery time interval (STI, ≥4 days; p=0.003) were independent factors correlating with higher TILs changes. CNB-LPBC patients showed better breast cancer-free interval (BCFI, p=0.021) than CNB-non-LPBC (CNB-nLPBC) patients. Patients were categorized into four groups according to the LPBC change pattern from CNB to SRS: LPBC→LPBC, LPBC→nLPBC, nLPBC→LPBC, and nLPBC→nLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBC→LPBC pattern was an independent prognostic factor of worse BCFI (hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.53; p=0.035) compared with other patterns.
Conclusion
TILs were significantly higher in SRS than in CNB. Higher TILs changes were associated with younger age and long STI. Changing from nLPBC to LPBC after CNB indicated a worse BCFI, which needs further validation.

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Anne Monette, Sarah Warren, J Carl Barrett, Charlie Garnett-Benson, Kurt A Schalper, Janis M Taube, Brian Topp, Alexandra Snyder
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Diagnostic performance of TILs–US score and LPBC in biopsy specimens for predicting pathological complete response in patients with breast cancer
Hideo Shigematsu, Kayo Fukui, Akiko Kanou, Erika Yokoyama, Makiko Tanaka, Mutsumi Fujimoto, Kanako Suzuki, Haruka Ikejiri, Ai Amioka, Emiko Hiraoka, Shinsuke Sasada, Akiko Emi, Tetsuya Nakagiri, Koji Arihiro, Morihito Okada
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Zuzana Kos, Elvire Roblin, Rim S. Kim, Stefan Michiels, Brandon D. Gallas, Weijie Chen, Koen K. van de Vijver, Shom Goel, Sylvia Adams, Sandra Demaria, Giuseppe Viale, Torsten O. Nielsen, Sunil S. Badve, W. Fraser Symmans, Christos Sotiriou, David L. Rimm
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Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?
Alexandra Caziuc, Diana Schlanger, Giorgiana Amarinei, George Calin Dindelegan
Journal of Clinical Medicine.2019; 8(4): 545. CrossRef

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Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil-Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer: Jieun Lee, Dong-Min Kim, Ahwon Lee; Cancer Res Treat. 2019;51(2):649-663. Published online July 31, 2018; DOI: https://doi.org/10.4143/crt.2018.270

Abstract PDF Supplementary Material PubReader ePub

Purpose
Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC).
Materials and Methods
Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain.
Results
Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002).
Conclusion
In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.

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Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers: Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee; Cancer Res Treat. 2019;51(1):80-89. Published online February 26, 2018; DOI: https://doi.org/10.4143/crt.2017.500

Abstract PDF PubReader ePub

Purpose
In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear.
Materials and Methods
We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts.
Results
In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041).
Conclusion
Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.

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Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancer
Alaknanda Adwal, Priyakshi Kalita-de Croft, Reshma Shakya, Malcolm Lim, Emarene Kalaw, Lucinda D Taege, Amy E McCart Reed, Sunil R Lakhani, David F Callen, Jodi M Saunus
Life Science Alliance.2020; 3(7): e201900562. CrossRef
Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors
Rom Keshet, Joo Sang Lee, Lital Adler, Muhammed Iraqi, Yarden Ariav, Lisha Qiu Jin Lim, Shaul Lerner, Shiran Rabinovich, Roni Oren, Rotem Katzir, Hila Weiss Tishler, Noa Stettner, Omer Goldman, Hadas Landesman, Sivan Galai, Yael Kuperman, Yuri Kuznetsov,
Nature Cancer.2020; 1(9): 894. CrossRef
Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer
Alexey V. Morozov, Vadim L. Karpov
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Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens
Aleksandra Wroblewska, Maxime Dhainaut, Benjamin Ben-Zvi, Samuel A. Rose, Eun Sook Park, El-Ad David Amir, Anela Bektesevic, Alessia Baccarini, Miriam Merad, Adeeb H. Rahman, Brian D. Brown
Cell.2018; 175(4): 1141. CrossRef

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Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area: Cheng Xu, Shi-Ping Yang, Yuan Zhang, Ling-Long Tang, Guan-Qun Zhou, Xu Liu, Yan-Ping Mao, Rui Guo, Wen-Fei Li, Lei Chen, Ai-Hua Lin, Ying Sun, Jun Ma; Cancer Res Treat. 2018;50(3):777-790. Published online July 24, 2017; DOI: https://doi.org/10.4143/crt.2017.255

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLR_min). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLR_min on OS/DFS.
Results
Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLR_min (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLR_min ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect.
Conclusion
Occurrence of neutropenia, number of myelosuppression events, and high post-NLR_min during PF/TP IC-1 have prognostic value for poor survival in LANPC.

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Associations between inflammatory biomarkers, symptoms, treatment toxicities and quality of life in people with advanced cancer receiving systemic anti-cancer treatments: a systematic review
Helen Andersen, Wei-Hong Liu, Patsy Yates, Morgan J. Farley, Kim E. Alexander
Supportive Care in Cancer.2026;[Epub] CrossRef
Development of a simplified population pharmacokinetic–pharmacodynamic framework for exposure-informed risk stratification of neutropenia during amrubicin treatment
Yoshinori Makino, Takanori Ogawa, Reiko Makihara–Ando, Naomi Sakiyama, Masahito Yamazaki, Chizuru Naito, Hiroki Takayama, Genji Ueda, Shunsuke Kohyama, Maki Todo, Yasuhiro Kuwata, Masataka Hirasaki, Tetsuya Hamaguchi
Cancer Chemotherapy and Pharmacology.2026;[Epub] CrossRef
The approach of hematologists toward managing neutropenic fever in patients with hematological malignancies: Insights from the Iraqi experience
Alaadin Sahham Naji, Luma Essa Hamodi, Alaa Fadhil Alwan, Ahmed Mjali
Iraqi Journal of Hematology.2025; 14(2): 243. CrossRef
Prospective clinical study of the efficacy and safety of different doses of PEG recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for preventing leukopenia/neutropenia caused by concurrent chemoradiotherapy for cervical cancer
Tingting Yu, Yiwei Zhang, Jiawen Li, Zhuo Li, Rui Tong
Holistic Integrative Oncology.2024;[Epub] CrossRef
Incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia in nasopharyngeal carcinoma
Lu‐Lu Zhang, Xi Chen, Ying‐Ying Huang, Chi‐Xiong Liang, Meng‐Yun Qiang, Zhuo‐Chen Cai, Ze‐Jiang Zhan, Ying Deng, Jia‐Yu Zhou, Hao‐Yang Huang, Xiang Guo, Xing Lv
Cancer Medicine.2023; 12(13): 14084. CrossRef
Chinese expert consensus on the application of pegylated recombinant human granulocyte colony‐stimulating factor during concurrent chemoradiotherapy (2023 edition)
Jun Wang, Baosheng Li
Precision Radiation Oncology.2023; 7(3): 150. CrossRef
Chinese expert consensus on the application of pegylated recombinant human granulocyte colony‐stimulating factor during concurrent chemoradiotherapy (2020 edition)
Jun Wang, Baosheng Li
Precision Radiation Oncology.2021; 5(1): 4. CrossRef
Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma
Yuanji Xu, Zijie Wu, Wangzhong Ye, Youping Xiao, Wei Zheng, Qinyan Chen, Penggang Bai, Zhizhong Lin, Chuanben Chen
BMC Cancer.2021;[Epub] CrossRef
Time-to-Event Supervised Genetic Algorithm Enables Induction Chemotherapy Decision Making for Nasopharyngeal Carcinoma
Demin Liu, Haojiang Li, Liyang Wu, Shuchao Chen, Tianqiao Zhang, Wenjie Huang, Guangying Ruan, Sai Li, Lizhi Liu, Hongbo Chen
IEEE Access.2021; 9: 98701. CrossRef
Prognostic value of post-radiotherapy neutrophil-to-lymphocyte ratio in locally advanced nasopharyngeal carcinoma
Dan Ou, Xiaoshen Wang, Mingyao Wu, Fen Xue, Yujiao Li, Chaosu Hu, Xiayun He
Strahlentherapie und Onkologie.2020; 196(3): 252. CrossRef
Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound
Wei Wang, Dong Luo, Junlin Chen, Jinyun Chen, Yi Xia, Wenzhi Chen, Yan Wang
Bioscience Reports.2020;[Epub] CrossRef
Overview of Hematopoietic Stem Cells in Systemic Cancer Treatment, Aging, Pregnancy, and Radiation Hormesis
Aleksei N. Shoutko
Advances in Molecular Imaging.2019; 09(02): 19. CrossRef

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Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model: Pawel Chrom, Rafal Stec, Lubomir Bodnar, Cezary Szczylik; Cancer Res Treat. 2018;50(1):103-110. Published online March 3, 2017; DOI: https://doi.org/10.4143/crt.2017.033

Abstract PDF Supplementary Material PubReader ePub

Purpose
The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.
Materials and Methods
This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R², Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.
Results
Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R², 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R², 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).
Conclusion
Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

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Bruce Li, Swati Sood, Melissa J. Huynh, Nicholas E. Power
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Diana Voskuil-Galoş, Tudor Călinici, Andra Piciu, Adina Nemeş
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Plasma carnitine, choline, γ-butyrobetaine, and trimethylamine-N-oxide, but not zonulin, are reduced in overweight/obese patients with pre/diabetes or impaired glycemia
Alia Snouper, Violet Kasabri, Nailya Bulatova, Maysa Suyagh, Monther Sadder, Khaldoun Shnewer, Ismail Yousef
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Ella Barkan, Camillo Porta, Simona Rabinovici-Cohen, Valentina Tibollo, Silvana Quaglini, Mimma Rizzo
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Aqua Asif, Vinson Wai-Shun Chan, Filzah Hanis Osman, Jasmine Sze-Ern Koe, Alexander Ng, Oliver Edward Burton, Jon Cartledge, Michael Kimuli, Naveen Vasudev, Christy Ralph, Satinder Jagdev, Selina Bhattarai, Jonathan Smith, James Lenton, Tze Min Wah
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Xiao Zhou, Guangcheng Luo
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Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma
Uiju Cho, Yeoun-Eun Sung, Min-Sik Kim, Youn-Soo Lee
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Prognostic value of glucose to lymphocyte ratio for patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A multi-institutional, propensity score matching cohort study
Jinliang Ni, Ziye Li, Wei Song, Houliang Zhang, Yidi Wang, Yifan Zhang, Haipeng Zhang, Guangcan Yang, Jun Xie, Keyi Wang, Bo Peng, Weipu Mao
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Yasser Ged, Alejandro Sanchez, Sujata Patil, Andrea Knezevic, Emily Stein, Stacey Petruzella, Kate Weiss, Cihan Duzgol, Joshua Chaim, Oguz Akin, Marina Mourtzakis, Michael T. Paris, Jessica Scott, Fengshen Kuo, Ritesh Kotecha, A. Ari Hakimi, Chung-Han Lee
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Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers: So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim; Cancer Res Treat. 2017;49(2):313-321. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.098

Abstract PDF PubReader ePub

Purpose
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers.
Materials and Methods
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.
Results
MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor.
Conclusion
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

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Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors
Mart van Rijthoven, Simon Obahor, Fabio Pagliarulo, Maries van den Broek, Peter Schraml, Holger Moch, Jeroen van der Laak, Francesco Ciompi, Karina Silina
Communications Medicine.2024;[Epub] CrossRef
The roles of tertiary lymphoid structures in chronic diseases
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Nature Reviews Nephrology.2023; 19(8): 525. CrossRef
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
Jing Zhang, Mingyue Fan, Chanjuan Jin, Zhaoying Wang, Yutong Yao, Yueru Shi, Xin Hu, Youzhong Wan
Archives of Biochemistry and Biophysics.2022; 727: 109346. CrossRef
Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination
Yi Wang, Chunzhao Li, Xiaohan Chi, Xijian Huang, Hua Gao, Nan Ji, Yang Zhang
Frontiers in Oncology.2022;[Epub] CrossRef
Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
Abrar I. Aljohani, Chitra Joseph, Sasagu Kurozumi, Omar J. Mohammed, Islam M. Miligy, Andrew R. Green, Emad A. Rakha
Breast Cancer Research and Treatment.2020; 181(3): 541. CrossRef
Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2019; 51(1): 80. CrossRef
Grade II/III Glioma Microenvironment Mining and Its Prognostic Merit
Jiawei Chen, Chongxian Hou, Peng Wang, Yong Yang, Dong Zhou
World Neurosurgery.2019; 132: e76. CrossRef
Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Scientific Reports.2017;[Epub] CrossRef

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Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma: Chi Hoon Maeng, Young Hyeh Ko, Do Hoon Lim, Eun Suk Kang, Joon Young Choi, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2017;49(1):92-103. Published online May 9, 2016; DOI: https://doi.org/10.4143/crt.2015.476

Abstract PDF PubReader ePub

Purpose
This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas.
Materials and Methods
Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT.
Results
Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response.
Conclusion
TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.

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Sandeep Singh, Dipesh, Supratik Sen, Abhay Kumar Singh, Manindra Bhushan, Benoy Kumar Singh, Raj Pal Singh, Anuj Vijay, Jaskaran Singh Sethi, Munish Gairola
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Yasmin Ahmed Aboelmagd, Hany Mohammed Hegab, Gihan Kamal Shams El Din, Mohamed Hamdy Attia, Gehad Hamada Fekry Hafez, Inas Abdel Moaty Mohamed Eid
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Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study: Hee Seung Kim, Hwa-Young Choi, Maria Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Hyun Hoon Chung, Yong Beom Kim, Yong Sang Song; Cancer Res Treat. 2016;48(1):250-258. Published online March 6, 2015; DOI: https://doi.org/10.4143/crt.2014.324

Abstract PDF PubReader ePub

Purpose
We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC).
Materials and Methods
The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes.
Results
Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted noncomplete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers.
Conclusion
CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

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Prognostic Significance of Retroperitoneal Lymphadenectomy, Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Primary Fallopian Tube Carcinoma: A Multicenter Study: Kemal Gungorduk, Ibrahim E. Ertas, Aykut Ozdemir, Emrah Akkaya, Elcin Telli, Salih Taskin, Mehmet Gokcu, Ahmet Baris Guzel, Tufan Oge, Levent Akman, Tayfun Toptas, Ulas Solmaz, Askın Dogan, Mustafa Cosan Terek, Muzaffer Sanci, Aydin Ozsaran, Tayup Simsek, Mehmet Ali Vardar, Omer Tarik Yalcin, Sinan Ozalp, Yusuf Yildirim, Firat Ortac; Cancer Res Treat. 2015;47(3):480-488. Published online November 17, 2014; DOI: https://doi.org/10.4143/crt.2014.058

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to evaluate the prognostic role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the need for para-aortic lymphadectomy in patients with primary fallopian tube carcinoma (PFTC). Materials and Methods Ninety-one patients with a diagnosis of PFTC were identified through the gynecologic oncology service database of six academic centers. Clinicopathological, surgical, and complete blood count data were collected. Results In univariate analysis, advanced stage, suboptimal surgery, and NLR > 2.7 were significant prognostic factors for progression-free survival, whereas in multivariate analysis, only advanced stage and suboptimal surgery were significant. In addition, in univariate analysis, cancer antigen 125 ≥ 35 m/IU, ascites, advanced stage, suboptimal surgery, NLR > 2.7, PLR > 233.3, platelet count ≥ 400,000 cells/mm3, staging type, and histological subtype were significant prognostic factors for overall survival (OS); however, in multivariate analysis, only advanced stage, suboptimal surgery, NLR > 2.7, and staging type were significant. Inclusion of pelvic and para-aortic lymphadenectomy in surgery showed significant association with longer OS, with a mean and median OS of 42.0 months and 35.5 months (range, 22 to 78 months), respectively, vs. 33.5 months and 27.5 months (range, 14 to 76 months), respectively, for patients who underwent surgery without para-aortic lymphadenectomy (hazard ratio, 3.1; 95% confidence interval, 1.4 to 5.7; p=0.002). Conclusion NLR (in both univariate and multivariate analysis) and PLR (only in univariate analysis) were prognostic factors in PFTC. NLR and PLR are inexpensive and easy tests to perform. In addition, patients with PFTC who underwent bilateral pelvic and para-aortic lymphadenectomy had longer OS.

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Case Report

Cyclosporine in Relapsed Subcutaneous Panniculitis-like T-Cell Lymphoma after Autologous Hematopoietic Stem Cell Transplantation: Hye Ryun Jung, So Yeon Yun, Jun Hyeok Choi, Sung Hwa Bae, Hun-Mo Ryoo, Yoon-Seup Kum; Cancer Res Treat. 2011;43(4):255-259. Published online December 27, 2011; DOI: https://doi.org/10.4143/crt.2011.43.4.255

Abstract PDF PubReader ePub

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare T-cell lymphoma characterized by involvement of the subcutaneous tissue of neoplastic T lymphocytes. SPTCL with hemophagocytic syndrome (HPS) is associated with an aggressive clinical course and treatment of SPTCL with HPS is not well established. Cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy is not successful in most patients suffering from SPTCL with HPS. The role of high dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) remains controversial. We report a case of relapsed SPTCL after CHOP chemotherapy and salvage chemotherapy followed by autologous HSCT, which had rapid improvement within weeks after cyclosporine and prednisolone. Immunosuppressive therapy may be an important and successful treatment option in SPTCL patients, even though they may have clinically aggressive disease.

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Chi-Ching Chen, Chieh-Lin Teng, Su-Peng Yeh
Annals of Hematology.2016; 95(5): 837. CrossRef
Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides
Meenal Kheterpal, Neha Mehta-Shah, Pooja Virmani, Patricia L. Myskowski, Alison Moskowitz, Steven M. Horwitz
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Zebras and hen's teeth: recognition and management of rare T and NK lymphomas
Neha Mehta–Shah, Steven Horwitz
Hematology.2015; 2015(1): 545. CrossRef
Cyclosporine A as a Primary Treatment for Panniculitis-like T Cell Lymphoma: A Case with a Long-Term Remission
Won Sup Lee, Ji-Hyen Hwang, Moon Jin Kim, Se-Il Go, Anna Lee, Haa-Na Song, Min Jeong Lee, Myung Hee Kang, Hoon-Gu Kim, Jeong-Hee Lee
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Original Articles

Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer: Min-Ho Park, Deok-Hwan Yang, Mi-Hyun Kim, Jae-Hong Jang, Yoon-Young Jang, Youn-Kyung Lee, Chun-Ji Jin, Than Nhan Nguyen Pham, Truc Anh Nguyen Thi, Mi-Seon Lim, Hyun-Ju Lee, Cheol Yi Hong, Jung-Han Yoon, Je-Jung Lee; Cancer Res Treat. 2011;43(1):56-66. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.56

Abstract PDF PubReader ePub

PURPOSE
Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
MATERIALS AND METHODS
alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
RESULTS
The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells.
CONCLUSION
Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.

Citations

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Dendritic Cell-Based Cancer Vaccines: The Impact of Modulating Innate Lymphoid Cells on Anti-Tumor Efficacy
Yeganeh Mehrani, Solmaz Morovati, Fatemeh Keivan, Soroush Sarmadi, Sina Shojaei, Diba Forouzanpour, Byram W. Bridle, Khalil Karimi
Cells.2025; 14(11): 812. CrossRef
Usefulness of IL-21, IL-7, and IL-15 conditioned media for expansion of antigen-specific CD8+ T cells from healthy donor-PBMCs suitable for immunotherapy
Julián A. Chamucero-Millares, David A. Bernal-Estévez, Carlos A. Parra-López
Cellular Immunology.2021; 360: 104257. CrossRef
Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications
Charles Shin, Sung Soo Kim, Yong Hwa Jo
Molecular Therapy - Oncolytics.2021; 22: 166. CrossRef
Enhanced Human T Lymphocyte Antigen Priming by Cytokine-Matured Dendritic Cells Overexpressing Bcl-2 and IL-12
Hui Zhang, Yu Wang, Qian-Ting Wang, Sheng-Nan Sun, Shi-You Li, Hong Shang, You-Wen He
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines
N. Dobrovolskienė, V. Pašukonienė, A. Darinskas, J.A. Kraśko, K. Žilionytė, A. Mlynska, Ž. Gudlevičienė, E. Mišeikytė-Kaubrienė, V. Schijns, W. Lubitz, P. Kudela, M. Strioga
Vaccine.2018; 36(29): 4171. CrossRef
Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives
João Constantino, Célia Gomes, Amílcar Falcão, Maria T. Cruz, Bruno M. Neves
Translational Research.2016; 168: 74. CrossRef
Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation
Reza Mirzaei, Azad Saei, Fatemeh Torkashvand, Bahareh Azarian, Ahmad Jalili, Farshid Noorbakhsh, Behrouz Vaziri, Jamshid Hadjati
Tumor Biology.2016; 37(8): 10893. CrossRef
Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic
My-Dung Hoang, Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Thanh-Nhan Nguyen-Pham, Nu-Ri Choi, Manh-Cuong Vo, Seung-Shin Lee, Jae-Sook Ahn, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Chonnam Medical Journal.2015; 51(1): 1. CrossRef
Dendritic Cells Induce Specific Cytotoxic T Lymphocytes against Prostate Cancer TRAMP-C2 Cells Loaded with Freeze-thaw Antigen and PEP-3 Peptide
Xiao-Qi Liu, Rong Jiang, Si-Qi Li, Jing Wang, Fa-Ping Yi
Asian Pacific Journal of Cancer Prevention.2015; 16(2): 571. CrossRef
Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI-SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization of Dendritic Cells
My-Dung Hoang, Hwa-Jeong Lee, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyeoung-Joon Kim, In-Kyu Park, Je-Jung Lee
Journal of Immunology Research.2015; 2015: 1. CrossRef
Generation of Potent Cytotoxic T Lymphocytes Against Castration‐Resistant Prostate Cancer Cells by Dendritic Cells Loaded With Dying Allogeneic Prostate Cancer Cells
E. C. Hwang, M.‐S. Lim, C.‐M. Im, D.‐D. Kwon, H.‐J. Lee, T.‐N. Nguyen‐Pham, Y.‐K. Lee, J.‐J. Lee
Scandinavian Journal of Immunology.2013; 77(2): 117. CrossRef
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Arpit Bhargava, Dinesh Mishra, Smita Banerjee, Pradyumna Kumar Mishra
Immunotherapy.2012; 4(7): 703. CrossRef

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Altered Expression of Smad Proteins in T or NK-cell Lymphomas: Jai Hyang Go; Cancer Res Treat. 2008;40(4):197-201. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.197

Abstract PDF PubReader ePub

Purpose

Smad proteins mediate cellular signaling through the transforming growth factor-β family (TGF-βs). Smads 2 and 3 transmit signals from TGF-β, and Smad4 is a common mediator, as well. However, little is known concerning the expression patterns of Smads in lymphoid tissue.

Materials and Methods

Immunohistochemistry for Smad3 and Smad4 was performed on paraffin-embedded tissue sections collected from 26 T- or NK-cell lymphomas.

Results

Nearly all cells in germinal centers were positive for Smad3, and more than 50% of paracortical cells were positive for Smad3 in reactive lymphoid tissue. When Smad4 immunostaining was conducted, nearly all the cells in the germinal centers showed diffuse cytoplasmic staining, and most of them exhibited nuclear positivity, as well. In addition, more than 50% of the cells in the paracortex were positive for Smad4. Furthermore, the Smad3 staining pattern was preserved in all malignant lymphomas, but four of these cases (15%) exhibited decreased expression of Smad4. All lymphoblastic lymphomas showed strong positivity in most of tumor cells, but one unspecified peripheral lymphoma, two nasal NK/T cell lymphomas, and one anaplastic large cell lymphoma were negative for Smad4.

Conclusions

These results suggest that TGF-β-specific Smads may be actively involved in signal transduction in lymphoid organs and that Smad-mediated TGF-β signaling pathways are operative in malignant lymphoma. In addition, loss of Smad4 expression might be associated with development of some T-cell lymphomas.

Citations

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Targeted Transcriptomic Profiling Identifies Biomarkers and Molecular Features Associated With Immunotherapy Response in Classic Hodgkin Lymphoma
Leticia Hamana, Mario L. Marques-Piubelli, Lu Wei, Khaja Khan, Lakshmi Kakarala, Li Shen, Ignacio I. Wistuba, Hun Ju Lee, Luisa M. Solis, Francisco Vega
Modern Pathology.2026; : 101060. CrossRef
Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review
Karen E. Wain, Marissa S. Ellingson, Jamie McDonald, Amanda Gammon, Maegan Roberts, Pavel Pichurin, Ingrid Winship, Douglas L. Riegert-Johnson, Jeffrey N. Weitzel, Noralane M. Lindor
Genetics in Medicine.2014; 16(8): 588. CrossRef
Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma
Chang Ohk Sung, Sang Cheol Kim, Sivasundaram Karnan, Kennosuke Karube, Hyung Jin Shin, Do-Hyun Nam, Yeon-Lim Suh, Seok-Hyung Kim, Ji Yeon Kim, Seok Jin Kim, Won Seog Kim, Masao Seto, Young-Hyeh Ko
Blood.2011; 117(4): 1291. CrossRef

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A Study of Fas / Fas - Expression and Apoptosis according to the Progression of Gastric Adenocarclnoma: Sung Chul Lim, Jeong Hwan Chang; J Korean Cancer Assoc. 1999;31(6):1101-1111.

Abstract PDF: PURPOSE
The purpose of this study was to determine whether Fas-L expression is associated with increased apoptotic induction of tumor-infiltrating lymphocytes (TIL) in human gastric carcinomas.
MATERIALS AND METHODS
The author analysed 38 cases of early gastric carcinoma (EGC) and 61 cases of advanced gastric carcinoma (AGC) who received gastric resection, in whom the number of diffuse type was 38 cases and the number of intestinal type was 61 cases. The author used immunohistochemical staining for Fas, Fas-L and CD45, and TUNEL in situ apoptosis detection kit. TIL were detected by CD45 and apoptosis of TIL were detected by CD45 expression and TUNEL positivity on serial histologic sections.
RESULTS
Fas-L was localized to neoplastic cells in 61% (23/38) of EGC group and 66% (40/61) of AGC group. The extent of Fas-L expression was variable, with both Fas-L positive and negative neoplastic region occuring within tumors. TIL adjacent to Fas-L expressing tumor region were decreased in number and TIL adjacent to FasL-negative tumor region were increased in number; apoptotic induction of TIL showed just the opposite pattern (p<0.05). Fas expression was found essentially homogeneously throughout the tumor mass independent of tumor stage. Fas expression showed 64% (39/61) of intestinal type and 68% (26/38) of diffuse type. Labeling indices for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively and this difference was statistically insignificant. Co-expression of Fas-L and Fas, which occurred over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. In addition, factors such as tumor stage and other prognostic factors were not concerned in Fas and Fas-L expression, number of TIL and apoptotic induction.
CONCLUSION
These findings suggest Fas-mediated apoptotic depletion of TIL in response to Fas-L expression by stomach cancers, and provide the evidence to support the Fas counterattack as a mechanism of immune escape in gastric cancer. In addition, gastric carcinoma cells of the intestinal and diffuse type did not differ in their expression of the apoptotic receptor Fas.

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The Study for the Postoperative Changes of Peripheral Lymphocytes and their Subsets as Immune Function in Advanced Gastric Cancer: Yoon Sun Joh, Yon Geul Joh, Min Young Cho, Sung Ock Suh; J Korean Cancer Assoc. 1999;31(5):946-954.

Abstract PDF: PURPOSE
This study evaluated the immunologic function of the postoperative lymphacytes and their subsets during 2 years after the curative resection of advanced gastric cancer.
MATERIALS AND METHODS
The peripheral lymphocytes and their subset in 64 advanced gastric cancer patients were preoperatively and postoperatively measured by using fluorescent conjugated monoclonal antibodies with flow cytometry. The monoclonal antibodies to T lymphocyte (CD3), B lymphocyte (CD19), helper-inducer cell (CD4), suppressor- cytotoxic cell (CD8), natural killer cell (CD16), and activated T cell (HLA-DR) antigens were used individually corresponding to T lymphocytes, B lymphocytes, helper-inducer T cells, suppressor-cytotoxic T cells, natural killer cells and activated T cells in post- operative periods (1, 3, 6, 12, 18, K 24 months). Their postoperative data were compared to the preoperative data in advanced gastric cancer.
RESULTS
On sequential measurements, peripheral lymphocytes were significantly decreased in postoperative 1 month than preoperative 1 day but they were gradually increased in postoperative 3, 6, 12, 18 and 24 months with significance. The B lymphocytes were significantly decreased in postoperative 3 and 6 months. NK cells were significantly increased in postoperative 3 months.
CONCLUSION
The two years postoperative changing patterns of peripheral lymphocytes and their subsets may not be improved in advanced gastric cancer patients which were undertaken curative surgery except lymphocyte.

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Distribution of Langerhans Cells Associated with T Lymphocytes in Primary Lung Cancer: Dong Hwan Shin, Kyung Young Chung, Byung Soo Kim, Kwang Hwa Park; J Korean Cancer Assoc. 1996;28(2):272-281.

Abstract PDF: We have studied the distribution of Langerhans cells associated with T lymphocytes/or histocytes in 83 cases of resected primary lung cancers by immunohistochemical methods using anti-S100 protein, B and T lymphocyte markers and anti-lysozyme antibodies. Langerhans cells were present in all the main histologic subtypes but small cell carcinoma. Langerhans cells were noted much more frequently in adenocarcinoma, particularly those subclassified as bronchioloalveolar carcinoma than in other histologic types. T lymphocytes were seen if any associated with Langerhans cells among tumor cells whereas lysozyme positive histiocytes were mostly scattered in the supporting stroma between tumor cells. Clinical follow-up data available for 72 cases showed no significant correlations between infiltration of Langerhans cells and overall survival. There seemed to be a little longer survival in adenocarcinoma with Langerhans cells than those without but it proved to be insignificant by statistical analysis. The current results remain to be confirmed in much larger studies with regard to prognostic significance of infiltrating Langerhans cells and their association with T lymphocytes in primary lung cancers in view of known immunologic role of Langerhans cells.

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IL-2 Induced Nitric Oxide Synthesis by Tumor Cells in Corultures of Lymphocytes and Tumor Cells: Chang Yeol Yim, Sang Youel Park, Wan Hee Yoo, Jae Yong Kwak, Soo Teik Lee, Myung Hee Sohn, Dae Ghon Kim, Deuk Soo Ahn; J Korean Cancer Assoc. 1999;31(2):339-347.

Abstract PDF: PURPOSE
Nitric oxide (NO) synthesis has been known to be induced during interleukin-2 (IL-2) therapy. The present study was designed to elucidate mechanisms and roles of IL-2-induced NO synthesis in tumor cells.
MATERIALS AND METHODS
Mechanisms of IL-2-induced NO synthesis were evaluated using in vitro culture systems of BALB/c mouse splenic lymphocytes and Meth-A tumor cells. Effects of IL-2-induced NO synthesis by Meth-A tumor cells on the tumor cell proliferation were also evaluated using an NO synthase inhibitor, N -monomethyl- L-arginine (MLA).
RESULTS
Cultures of both lymphocytes alone and Meth-A tumor cells alone did not produce any significant amounts of nitrite, a stable metabolite of NO during IL-2 stimulation. In contrast, cocultures of lymphocytes and Meth-A tumor cells produced a large amount of nitrite during IL-2 stimulation. Addition of culture supernatants of lymphocytes incubated with IL-2 induced nitrite production in Meth-A tumor cell cultures. However, addition of culture supernatants of Meth-A tumor cells incubated with IL-2 did not induce nitrite production in lymphocyte cultures. Nitrite accumulation was markedly inhibited by addition of anti-interferon-y antibody, confirming the role of the cytokine in mediating tumor cell NO synthesis. MLA inhibited nitrite production by Meth-A tumor cells in a dose-dependent manner in the presence of culture supernatants of lymphocytes incubated with IL-2. Meth-A tumor cell nitrite production in the presence of increasing concentrations of MLA correlated inversely with tumor cell proliferation.
CONCLUSION
NO synthesis can be induced by tumor cells by the secondarily released cytokines from lymphocytes during IL-2 stimulation. Autologous NO synthesized by tumor cells during IL-2 stimulation inhibits proliferation of tumor cells themselves.

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A Case of Well - Differentiated Thymic Carcinoma with Severe Aplastic Anemia: Jung Ah Kim, Gi Hyeon Seo, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Keun Chil Park, Young Hyeh Ko, Chan Hyung Park; J Korean Cancer Assoc. 1996;28(5):897-903.

Abstract PDF: Thymoma is occasionally associated with hematologic disorders such as pure red cell aplasia, agranulocytosis, and thrombocytopenia and several cases have been associated with pancytopenia. In contrast, thymic carcinoma has rarely been associated with aplastic anemia except one case reported by Thomas et aL. This case report concerns a patient in whom we have observed simultaneous occurrence of a well differentiated thymic carcinoma and a severe marrow aplasia for which we describe our therapeutic approach. Our patient did not benefit from thymectomy. We then tried antilymphocyte globulin and cyclosporine and the patient had a partial response with hematologic improvements.

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Immunologic and Oncogenic Study on the Cervical Neoplasia: Eun Yeong Seol, Sung Chul Lim; J Korean Cancer Assoc. 1996;28(6):1071-1083.

Abstract PDF: Immune response commonly is cited as a determining factor in the development or clearance of various neoplasias, but the immunobiology of neoplastic progression is poorly understood. The cervix has the largest concentration of lymphocytes found in the female genital tract and as a component of the common mucosal immune system guards against ascending infection from the microbial-laiden vagina, but cervical immunocytes have not been well characterized in the neoplasia itself. The objective of this study is to characterize the subpopulations of lymphocytes that infiltrate various grades of cervical neoplasia including metaplasia to invasive carcinoma. To establish the correlation I examined 60 cases of uterine cervix which were divided 4 categories according to the Bethesda Classification system; normal cervix(15), low grade squamous intraepithelial lesions(SILs)(15), high grade SILs(15), and invasive squamous cell carcinomas(15 cases). The degrees of T-lymphocyte infiltration were assessed after immunohistochemical staining by UCHL1, and compared to stainability of aberrant p53 and bcl-2 protein. There were significant increasing number and proportion of T-cells of invaisve cancers compared with that of preinvasive lesions. Aberrant p53 expression of invasive cancer was a little more intensive than that of low grade and high grade SILs, and there was no correlation between T-cell infiltration and aberrant p53 and/or bcl-2 expression. Bcl-2 was expressed in most of basal layer and some cases of parabasal layer of low and high grade SILs, and some minute foci of invasive cancer. In the adjacent areas of SILs and invasive lesions strong bcl-2 expression was noted in parabasal, intermediate or superficial cells case by case. In conclusion, the UCHLl-positive T cell infiltrate far exceeded in the invasive, but not in the preinvasive lesions, a finding that suggests that T cells are recruited preferentially to cervical lesions with progression to invasion. It is suggested that the T cell recruitment is not related to p53 or bc1-2, but the unknown third factors, and the bcl-2 overexpression is involved in the early step of epithelial neoplastic transforrnation and followed by recurrent overexposure to various oncogenic factors.

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