Cancer Research and Treatment

Original Articles

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 [Accepted]

Abstract PDF Supplementary Material: 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 cella 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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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; Received June 19, 2025 Accepted August 12, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.641 [Accepted]

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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Anticancer Treatment Influences TREM2 in Tumor-Associated Macrophages in Lung Cancer: Yoon Jin Cha, Eun Hye Lee, Chi Young Kim, Yong Jun Choi, Min Kyung Park, Sang Hoon Lee, Eun Young Kim, Yoon Soo Chang; Received December 26, 2024 Accepted June 22, 2025 Published online June 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1245 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME.
Materials and Methods
Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them.
Results
Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells.
Conclusion
Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

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Breast cancer

Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis: Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha; Cancer Res Treat. 2026;58(1):182-197. Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.033

Abstract PDF Supplementary Material PubReader ePub: Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Methods
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

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Lung and Thoracic cancer

Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma: Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou; Cancer Res Treat. 2025;57(4):1000-1018. Published online January 20, 2025; DOI: https://doi.org/10.4143/crt.2024.1119

Abstract PDF Supplementary Material PubReader ePub

Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
One thousand one hundred thirty LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA sequencing (RNA-seq), experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% confidence interval, 0.729 to 0.804). Additionally, we identified acyl-CoA synthetase long-chain family member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (p < 0.001) and overall survival (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon-α secretion, as indicated by bulk RNA-seq and enzyme-linked immunosorbent assay analysis, thereby promoting the infiltration of antitumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.

Citations

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Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment
Rundong Liu, Chendong Wang, Zhen Tao, Guangyuan Hu
Biomedicines.2025; 13(8): 1895. CrossRef
Independent validation of lung adenocarcinoma prognostic risk scores incorporating cholesterol and estrogen metabolism related transcriptional biomarkers
Qian Zhu, Yuemei Zhang, Jian Ma, Yongjia Li, Hongya Liu, Zhongwen Gong, Ming Du, Xuemei Lian
Scientific Reports.2025;[Epub] CrossRef
Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets
Xiaoliang Deng, Yanqun Luo, Ying Gao, Tao Wu
Molecular Biomedicine.2025;[Epub] CrossRef

3,919 View
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Review Article

Applicability of Spatial Technology in Cancer Research: Sangjeong Ahn, Hye Seung Lee; Cancer Res Treat. 2024;56(2):343-356. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1302

Abstract PDF PubReader ePub

This review explores spatial mapping technologies in cancer research, highlighting their crucial role in understanding the complexities of the tumor microenvironment (TME). The TME, which is an intricate ecosystem of diverse cell types, has a significant impact on tumor dynamics and treatment outcomes. This review closely examines cutting-edge spatial mapping technologies, categorizing them into capture-, imaging-, and antibody-based approaches. Each technology was scrutinized for its advantages and disadvantages, factoring in aspects such as spatial profiling area, multiplexing capabilities, and resolution. Additionally, we draw attention to the nuanced choices researchers face, with capture-based methods lending themselves to hypothesis generation, and imaging/antibody-based methods that fit neatly into hypothesis testing. Looking ahead, we anticipate a scenario in which multi-omics data are seamlessly integrated, artificial intelligence enhances data analysis, and spatiotemporal profiling opens up new dimensions.

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Navigating the landscape of plant proteomics
Tian Sang, Zhen Zhang, Guting Liu, Pengcheng Wang
Journal of Integrative Plant Biology.2025; 67(3): 740. CrossRef
Benchmarking computational methods for detecting spatial domains and domain-specific spatially variable genes from spatial transcriptomics data
Liping Kang, Qinglong Zhang, Fan Qian, Junyao Liang, Xiaohui Wu
Nucleic Acids Research.2025;[Epub] CrossRef
The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): Emerging therapeutic opportunities
Hussein Sabit, Amro Adel, Mariam M. Abdelfattah, Rehab M. Ramadan, Mahmoud Nazih, Shaimaa Abdel-Ghany, Ahmed El-hashash, Borros Arneth
Cancer Letters.2025; 628: 217865. CrossRef
Molecular pathobiology of breast fibroepithelial tumours
R.M.H. Lim, S. Haghani, H.Y. Tay, B.Y. Lim, B. Kannan, T.K. Ko, N.D. Md Nasir, B.T. Teh, P.H. Tan, J.Y. Chan
ESMO Rare Cancers.2025; 3: 100028. CrossRef
Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma
Yoonjin Kwak, Soo Kyung Nam, Yujun Park, Yun-Suhk Suh, Sang-Hoon Ahn, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Hyung-Ho Kim, Han-Kwang Yang, Hye Seung Lee
Modern Pathology.2024; 37(10): 100568. CrossRef
Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer
Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang
Cancer Research and Treatment.2024; 56(4): 1146. CrossRef
Prognostic significance of CD8 and TCF1 double positive T cell subset in microsatellite unstable gastric cancer
Juhyeong Park, Soo Kyung Nam, Yoonjin Kwak, Hyeon Jeong Oh, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
Scientific Reports.2024;[Epub] CrossRef

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Original Articles

Gastrointestinal cancer

A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer: Ting Liu, Qing Li, Zhen Lin, Chunhua Liu, Wei Pu, Shasha Zeng, Jun Lai, Xuebin Cai, Lisha Zhang, Shuyang Wang, Miao Chen, Wei Cao, Hongfeng Gou, Qing Zhu; Cancer Res Treat. 2024;56(2):602-615. Published online October 12, 2023; DOI: https://doi.org/10.4143/crt.2023.726

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.
Materials and Methods
Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m² nab-paclitaxel, 800 mg/m² gemcitabine, and 25 mg/m² cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.
Results
After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients.
Conclusion
In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

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Prognostic Value of FDG PET/CT Parameters in Patients With Advanced Biliary Tract Cancer Receiving Gemcitabine, Cisplatin, and Nab-Paclitaxel
Jeong Won Lee, Sang Mi Lee, Beodeul Kang, Jung Sun Kim, Jung Eun Kim, Hong Jae Chon, Su Jin Jang
Clinical Nuclear Medicine.2026;[Epub] CrossRef
Combined Chemotherapy-Immunotherapy for Advanced Biliary Tract Cancer (BTC): A Clinical, Genomic, and Biomarker Analysis
Yong Zhang, Miaomiao Gou
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Precision medicine for advanced biliary tract cancer in China: current status and future perspectives
Zhen Huang, Wen Zhang, Yongkun Sun, Dong Yan, Xijie Zhang, Lu Liang, Hong Zhao
Frontiers of Medicine.2025; 19(5): 743. CrossRef
Efficacy and biomarker analysis of second‐line nab‐paclitaxel plus sintilimab in patients with advanced biliary tract cancer
Xiaofen Li, Nan Zhou, Yu Yang, Zijian Lu, Hongfeng Gou
Cancer Science.2024; 115(7): 2371. CrossRef

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4 Web of Science
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Lung and Thoracic cancer

Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer: Hyun-Seock Shin, Juwhan Choi, Jinhwan Lee, Sung Yong Lee; Cancer Res Treat. 2022;54(2):458-468. Published online September 10, 2021; DOI: https://doi.org/10.4143/crt.2021.425

Abstract PDF Supplementary Material PubReader ePub

Purpose
Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.
Materials and Methods
The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.
Results
The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.
Conclusion
HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

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Lysosomes: guardians and healers within cells- multifaceted perspective and outlook from injury repair to disease treatment
Jianlei Bi, Yincong Sun, Meihua Guo, Xiaoxin Sun, Jie sun, Rujiao Jiang, Ning Wang, Gena Huang
Cancer Cell International.2025;[Epub] CrossRef
Recent advances in biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer
Jiacheng Zhang, Zehao Song, Yuanjie Zhang, Chentong Zhang, Qi Xue, Guochao Zhang, Fengwei Tan
Frontiers in Immunology.2025;[Epub] CrossRef
Combination of HDAC inhibition and cytokine enhances therapeutic HPV vaccine therapy
Lisa K Poppe, Nicholas Roller, Miriam Marlene Medina-Enriquez, Wiem Lassoued, Daniel Burnett, Katherine E Lothstein, Asma S Khelifa, Masaya Miyamoto, James L Gulley, Caroline Jochems, Jeffrey Schlom, Sofia R Gameiro
Journal for ImmunoTherapy of Cancer.2025; 13(5): e011074. CrossRef
Histone modifications and metabolic reprogramming in tumor-associated macrophages: a potential target of tumor immunotherapy
Yiting Xu, Han Zhang, Dengyun Nie
Frontiers in Immunology.2025;[Epub] CrossRef
Death-ision: the link between cellular resilience and cancer resistance to treatments
Gustavo Baldassarre, Ivana L. de la Serna, François M. Vallette
Molecular Cancer.2025;[Epub] CrossRef
Adverse drug reaction profiles of histone deacetylase inhibitors
Ruqayyah Begum, Jason L. Parsons, Alan M. Jones
Scientific Reports.2025;[Epub] CrossRef
Immunomodulatory properties of HDAC6 inhibitors in cancer diseases: New chances for sophisticated drug design and treatment optimization
Bernhard Biersack, Bianca Nitzsche, Michael Höpfner
Seminars in Cell & Developmental Biology.2024; 154: 286. CrossRef
Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1
Ana Dillen, Indy Bui, Megan Jung, Stephanie Agioti, Apostolos Zaravinos, Benjamin Bonavida
Cancers.2024; 16(6): 1237. CrossRef
Reducing PD-L1 Expression by Degraders and Downregulators as a Novel Strategy to Target the PD-1/PD-L1 Pathway
Zhijie Wang, Lin Yuan, Xiaotong Liao, Xia Guo, Jianjun Chen
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Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells
Sarah Ducellier, Mélanie Demeules, Boris Letribot, Massimiliano Gaetani, Chloé Michaudel, Harry Sokol, Abdallah Hamze, Mouad Alami, Mégane Nascimento, Sébastien Apcher
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Tsutomu Anraku, Masaki Murata, Hiroo Kuroki, Akira Kazama, Yuko Shirono, Masayuki Tasaki, Vladimir Bilim, Yoshihiko Tomita
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Mohammad-Salar Hosseini, Zohreh Sanaat, Mohammad Amin Akbarzadeh, Yosra Vaez-Gharamaleki, Mahsa Akbarzadeh
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Hikaru Nanamori, Yu Sawada
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Shuo Yang, Yang Huang, Qi Zhao
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International Journal of Oncology.2022;[Epub] CrossRef

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Lymphoma

Forkhead Box C1 (FOXC1) Expression in Stromal Cells within the Microenvironment of T and NK Cell Lymphomas: Association with Tumor Dormancy and Activation: Ji Hae Nahm, Woo Ick Yang, Sun Och Yoon; Cancer Res Treat. 2020;52(4):1273-1282. Published online July 3, 2020; DOI: https://doi.org/10.4143/crt.2020.032

Abstract PDF Supplementary Material PubReader ePub

Purpose
Forkhead box C1 (FOXC1) is critical for maintaining bone marrow microenvironments during hematopoiesis, but its role in hematological malignancies remains obscure. Here, we investigated whether FOXC1 regulates tumor dormancy and activation in the microenvironments of T and natural killer (NK) cell lymphomas.
Materials and Methods
One hundred and twenty cases of T and NK cell lymphomas were included; the immunohistochemical expression of FOXC1 was investigated in stromal cells, and numbers of FOXC1⁺ stromal cells were counted. Furthermore, the expression of phosphorylated p38 (p-p38) and phosphorylated ERK1/2 (p-ERK1/2) in tumor cells was investigated using immunohistochemistry.
Results
FOXC1 was variably expressed in C-X-C motif chemokine 12–associated reticular stromal cells, histiocytes, (myo)fibroblasts, and endothelial cells. The phenotypes of cases were categorized as dormant (high p-p38/low p-ERK1/2; n=30, 25.0%), active (high p-ERK1/2/low p-p38; n=25, 20.8%), or intermediate (others; n=65, 54.2%). Lower FOXC1⁺ stromal cell infiltration was associated with the dormant phenotype, the precursor T lymphoblastic leukemia/lymphoma subtype, and inferior overall survival rates, whereas higher FOXC1⁺ stromal cell infiltration was associated with the active phenotype and favorable patient prognosis (p < 0.05 for all).
Conclusion
These results suggested that FOXC1⁺ stromal cells within the microenvironments of T and NK cell lymphomas might be related to tumor phenotypes.

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Mechanisms of lymphoma-stromal interactions focusing on tumor-associated macrophages, fibroblastic reticular cells, and follicular dendritic cells
Rintaro Ohe
Journal of Clinical and Experimental Hematopathology.2024; 64(3): 166. CrossRef

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5 Web of Science
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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment: Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim; Cancer Res Treat. 2020;52(1):98-108. Published online May 27, 2019; DOI: https://doi.org/10.4143/crt.2019.195

Abstract PDF PubReader ePub

Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

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Jianchao Wang, Wenfang Zhang, Jiyang Zhang, Chenhui Zhao, Wei Zhang, Menghan Fang, Fangfang Chen, Zhida Wu, Xiaoya Xu, Ziqing Yu, Qiong Zhu, Yi Shi, Dadong Zhang, Xiaofeng Chen, Gang Chen
Advanced Science.2026;[Epub] CrossRef
Exploring Multiplex Immunohistochemistry (mIHC) Techniques and Histopathology Image Analysis: Current Practice and Potential for Clinical Incorporation
Aria Kaiyuan Sun, Song Fan, Siu Wai Choi
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The immunologic phenotype of thrombi is associated with future vascular events after cerebral infarction
Wookjin Yang, Soon Auck Hong, Jeong-Min Kim, Hae-Bong Jeong, Taek-Kyun Nam, Hyun Ho Choi, Suh Min Kim, Kwang-Yeol Park, Hye Ryoun Kim
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Lei Jiang, Xingwang Zhao, Yilin Li, Yajie Hu, Yu Sun, Shengde Liu, Zizhen Zhang, Yanyan Li, Xujiao Feng, Jiajia Yuan, Jian Li, Xiaotian Zhang, Yang Chen, Lin Shen
IUBMB Life.2024; 76(7): 420. CrossRef
HCR spectral imaging: 10-plex, quantitative, high-resolution RNA and protein imaging in highly autofluorescent samples
Samuel J. Schulte, Mark E. Fornace, John K. Hall, Grace J. Shin, Niles A. Pierce
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iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice
Jihye Kim, Jee Hyun Kim, Younghoon Kim, Jooyoung Lee, Hyun Jung Lee, Seong-Joon Koh, Jong Pil Im, Joo Sung Kim
Histochemistry and Cell Biology.2024; 162(5): 415. CrossRef
Immunohistochemistry for assessing toxicity and mechanism of action of anticancer drugs during preclinical trials. From theory to practice
M. A. Dodokhova, M. A. Akimenko, O. V. Voronova, M. S. Alkhusein-Kulyaginova, N. A. Kornienko, M. V. Gulyan, D. N. Gyulmamedov, M.-M. Kh. Alasheva, E. Sh. Kazimagomedova, D. B. Shpakovsky, E. R. Milaeva, I. M. Kotieva
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Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer
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Automatic generation of pathological benchmark dataset from hyperspectral images of double stained tissues
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