Cancer Research and Treatment

Original Articles

Real World Efficacy and Safety of First Line Chemo Immunotherapy in Extensive Stage Small Cell Lung Cancer and its association with molecular subtype: Miran Han, Sehhoon Park, Se-Hoon Lee, Junkyu Kim, Jin-yong Kim, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn; Received September 3, 2025 Accepted November 4, 2025 Published online November 5, 2025; DOI: https://doi.org/10.4143/crt.2025.971 [Accepted]

Abstract PDF: Purpose
Small cell lung cancer (SCLC) is an aggressive malignancy with poor outcomes. IMpower133 and CASPIAN established platinum–etoposide plus anti–PD-L1 antibody as standard first-line therapy for extensive-stage SCLC (ES-SCLC). Real-world data in Korean patients are scarce. We evaluated the effectiveness and safety of first-line chemo-immunotherapy in ES-SCLC and compared outcomes with pivotal trials.
Materials and Methods
We retrospectively reviewed patients diagnosed with ES-SCLC between 2018 and 2021. Overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT) were analyzed using Kaplan–Meier methods. Multivariate Cox regression identified prognostic factors. Objective response rate (ORR) was assessed by RECIST v1.1, and histological subtypes evaluated.
Results
Among 177 patients, median age was 66 years (range, 42–91), with 63.8% aged ≥65; most were male (92.7%) and ECOG 0–1 (91.5%). Smoking history was present in 80.8%. Baseline brain and liver metastases occurred in 27.7% and 26%. Median follow-up was 27.2 months (range, 3.9–43.2). ORR was 74.5% (95% CI, 67.1–81.1). Median OS, PFS, and TTNT were 12.4 (95% CI, 11.6–14.9), 5.3 (95% CI, 5.1–5.87), and 5.6 months (95% CI, 1.43–38.27). In 49 patients with brain metastases, ORR was 63.2%, with no difference in efficacy. Local therapy for brain metastases improved OS (HR 0.42; p=0.012), while PFS was not different. Treatment-related adverse events occurred in 90%, primarily grade ≥2 cytopenias; the most common immune-related event was grade 1 rash.
Conclusion
In this real-world Korean cohort, first-line chemo-immunotherapy achieved outcomes comparable to pivotal trials, supporting its role as standard care for ES-SCLC in clinical practice.

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Phase 1 Study of IMC-002, a Next-Generation Anti-CD47 Antibody, in Advanced Solid Tumors: Jin Seok Ahn, Jung Yong Hong, Joon Oh Park, Sung Young Lee, SuYeon Kim, Hwi-yeol Yun, Chan-Young Ock, Woochan Hwang, Sung Ho Kim, Heung Tae Kim, Ho Yeong Lim; Received August 4, 2025 Accepted November 3, 2025 Published online November 4, 2025; DOI: https://doi.org/10.4143/crt.2025.820 [Accepted]

Abstract PDF: Purpose
IMC-002 is a fully human cluster of differentiation 47-targeted immunoglobulin G4 monoclonal antibody, designed to minimize off-target effects. This study (NCT05276310) assessed its safety/tolerability and preliminary anti-tumor activity in patients with advanced solid tumors who were not eligible for or had progressed on standard treatment.
Materials and Methods
Here we report results from the initial 3 + 3 design dose-escalation part of a two-part Phase 1, open-label, dose-escalation/expansion study. IMC-002 was administered intravenously every 2 weeks at four doses (5, 10, 20, and 30 mg/kg). The primary objective was to assess safety/tolerability, including maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Secondary objectives included pharmacokinetics and clinical activity, including best overall response (BOR), disease control rate (DCR), and clinical benefit rate (CBR).
Results
Twelve patients were included in total, with three per dose level. Most patients (11/12) had stage IV disease; 7/12 had received three prior systemic therapies. No dose-limiting toxicities were observed and MTD was not reached. The most common treatment-related adverse events (TRAEs) were rash (9/12), vitreous floaters (8/12), and (hemolytic) anemia (5/12). There was no treatment-related thrombocytopenia, neutropenia, or infection. IMC-002 had dose-proportional pharmacokinetics, achieving steady state levels from Cycle 2. BOR was stable disease in six patients (DCR 50.0%). CBR was 33% (four patients maintaining disease control for ≥6 months).
Conclusion
IMC-002 demonstrated favorable safety/tolerability at doses of 5–30 mg/kg every 2 weeks. RP2D was defined as 20 mg/kg every 3 weeks. Preliminary anti-tumor activity was observed, with a CBR of 33%.

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Analysis of T Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients: Tae-Yong Kim, Jeesun Yoon, Dae-Won Lee, Yoonjin Kwak, Hye Seung Lee, Do-Youn Oh; Received April 28, 2025 Accepted September 7, 2025 Published online September 9, 2025; DOI: https://doi.org/10.4143/crt.2025.458 [Accepted]

Abstract PDF: Purpose
As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).
Materials and Methods
Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.
Results
The proportions of patients with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6% and 88.1%. A high cytotoxic T-cell (T_cyto) density was related to longer overall survival (OS). GC with a high ratio of T_cyto/total T-cells (T_total) and a low ratio of regulatory T-cells (T_reg)/T_total showed better OS. A high density of PD-1- or TIM-3- expressing T_cyto were also associated with longer OS than a low density of those. Among memory T-cells (T_mem) subsets, GC with a high ratio of memory T_cyto/T_mem and a low ratio of memory T_reg/T_mem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of T_cyto/T_total and memory T_cyto/T_mem.
Conclusion
T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1- or TIM-3 expressing T-cells were also associated with response to ICIs, while memory T-cells subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.

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Review Article

Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application: Taerim Oh, Minwoo Kim, Gi-Sue Kang, Sung-Joon Ye, Changhoon Choi, Won Park, Michael Hay, Hiroshi Hirata, G-One Ahn; Received February 21, 2025 Accepted April 28, 2025 Published online April 29, 2025; DOI: https://doi.org/10.4143/crt.2025.200 [Epub ahead of print]

Abstract PDF: It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

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Original Articles

Neoadjuvant Sintilimab Combined with Gemcitabine and Cisplatin for Muscle-Invasive Bladder Cancer Patients Followed by Selective Bladder Sparing Surgery: A Phase 2 Trial: Zhou Tong, Guanghou Fu, Feng Zhou, Xiaoyan Liu, Xing Xue, Hangyu Zhang, Yimin Wang, Xudong Zhu, Yang Gao, Lulu Liu, Xuanwen Bao, Yi Zheng, Weijia Fang, Peng Zhao, Baiye Jin; Received February 24, 2025 Accepted April 22, 2025 Published online April 28, 2025; DOI: https://doi.org/10.4143/crt.2025.214 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery.
Materials and Methods
Patients with histopathological confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m² and cisplatin 35 mg/m² once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety.
Results
From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events.
Conclusion
Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

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Cost-Effectiveness Analysis of Daratumumab Monotherapy and Subsequent Therapies in Heavily Treated Relapsed/Refractory Multiple Myeloma: A Feasible Methodology using a Korean Nationwide Population Cohort: Sung-Soo Park, Suein Choi, Seungpil Jung, Seunghoon Han, Chaehyeon Lee, Jinseon Han, Soyoung Kim, Kihyun Kim, Chang-Ki Min; Received January 10, 2025 Accepted April 13, 2025 Published online April 15, 2025; DOI: https://doi.org/10.4143/crt.2025.046 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
High-cost novel therapies for multiple myeloma (MM) require evaluation of efficacy and cost-effectiveness.
Materials and Methods
This study developed a methodology to assess cost-effectiveness using nationwide data from 11,450 newly diagnosed MM patients. A novel algorithm was applied to identify lines of therapy (LoT).
Results
The number of newly diagnosed MM patients increased significantly, from 873 in 2010 to 1,464 in 2019 (p < 0.001). Advancing LoT was associated with shorter time to next treatment (TTNT) and overall survival (OS) (p < 0.001), while all-cause medical costs increased with each LoT (p < 0.001). Bortezomib-melphalan-prednisolone was the most common frontline regimen for transplant-ineligible patients (29.2%), while bortezomib-thalidomide-dexamethasone was most used for transplant-eligible patients (11.3%). Daratumumab monotherapy demonstrated superior second TTNT (7.8 vs. 5.2 months) and OS (8.5 vs. 5.3 months) compared to standard care in heavily treated MM patients, with statistical significance maintained after cost adjustment. For subsequent therapies following daratumumab, a methodology was developed to estimate required medical costs using the incremental cost-effectiveness ratio (ICER): Expected cost ($)=ICER×(Expected life expectancy–0.567)+35,601.
Conclusion
This study provides a novel cost-effectiveness framework linking treatment efficacy and real-world costs, supporting predictions of societal costs for future MM therapies.

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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

Citations to this article as recorded by

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

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Hematologic malignancy

Real-World Effectiveness and Safety of Intravenous Daratumumab in Patients with Multiple Myeloma: A Multicenter, Observational Study from Korea: Youngil Koh, Sung-Soo Yoon, Kihyun Kim, Je-Jung Lee, Sung-Hoon Jung, Sang Eun Yoon, Sung-Soo Park, YoungJu Park, Soomin Yoon, Chang-Ki Min; Cancer Res Treat. 2025;57(3):883-890. Published online December 24, 2024; DOI: https://doi.org/10.4143/crt.2024.781

Abstract PDF Supplementary Material PubReader ePub: Purpose
Daratumumab is a novel, first-in-class monoclonal antibody approved for use as monotherapy and in combination with other treatments for patients with multiple myeloma (MM). The aim of this observational study was to evaluate the effectiveness and safety of daratumumab in real-world clinical practice.
Materials and Methods
This observational multicenter study collected data from patients with MM treated in Korea between June 1, 2018, and February 28, 2022.
Results
A total of 125 patients with a diagnosis of MM were included and followed until discontinuation or completion of 52 weeks’ follow-up. The median age was 67 years, and 97.6% of patients received more than three prior lines of therapy. The overall response rate was 52.5% (95% confidence interval [CI], 43.2 to 61.8), and a very good partial response was observed in 19.5% of patients (95% CI, 12.8 to 27.8). Of the patients who achieved a partial or higher response (52.5%), the median time to first response was 2.4 months (95% CI, 1.8 to 3.4), and the median time from start of daratumumab treatment until progressive disease was 4.1 months (95% CI, 2.9 to 5.1). Fever (24.0%) was the most frequently recorded adverse event (AE), while anemia (8.8%) and neutropenia (8.0%) were the most frequently observed grade 3-4 AEs. Overall, no unexpected safety signals were observed.
Conclusion
In a rapidly evolving treatment landscape, this analysis provides insight into the real-world outcomes for patients with MM receiving daratumumab in Korea and reveals that real-world outcomes were improved over results demonstrated in a clinical trial setting.

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Head and Neck cancer

Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy: Eun Joo Kang, Shinwon Hwang, Yun-Gyoo Lee, Jong-Kwon Choi, Seong Hoon Shin, Yoon Hee Choi, Keun-Wook Lee, Hyun Woo Lee, Min Kyoung Kim, Seung Taek Lim, Hwan Jung Yun, Sang-Gon Park, Sangwoo Kim, Sung-Bae Kim, Hye Ryun Kim; Cancer Res Treat. 2025;57(3):709-719. Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836

Abstract PDF PubReader ePub: Purpose
Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).
Results
TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion
TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

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Lung and Thoracic cancer

Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study: Naoya Nishioka, Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama; Cancer Res Treat. 2025;57(2):412-421. Published online October 25, 2024; DOI: https://doi.org/10.4143/crt.2024.748

Abstract PDF Supplementary Material PubReader ePub

Purpose
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

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TTF-1 Negativity Predicts Poor Outcomes in Advanced Non-Squamous NSCLC Also in the Immunotherapy Era: A Multicenter Cohort Study and Meta-Analysis
Leonardo Brunetti, Valentina Santo, Alessandro Galletti, Alain Gelibter, Antonio Lugini, Gian Paolo Spinelli, Daniele Santini, Alessio Cortellini, Alessia Vendittelli, Giuseppina Rita Di Fazio, Fabrizio Citarella, Giulia La Cava, Emanuele Claudio Mingo, M
Cancers.2025; 17(13): 2188. CrossRef
The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma
Hiroyuki Yamada, Hiromu Yano, Eri Matsubara, Shukang Zhao, Yusuke Shinchi, Cheng Pan, Takamasa Koga, Kosuke Fujino, Yukio Fujiwara, Koei Ikeda, Yoshihiro Komohara, Makoto Suzuki
Human Cell.2025;[Epub] CrossRef
TTF‑1 expression is associated with survival in patients with non‑squamous non‑small cell lung cancer treated with immune checkpoint inhibitor therapy
Nozomu Murayama, Minehiko Inomata, Daisuke Furukawa, Moe Hashizume, Naoki Takata, Zenta Seto, Kotaro Tokui, Seisuke Okazawa, Shingo Imanishi, Toshiro Miwa, Ryuji Hayashi, Kohji Takagi, Kenichi Hirabayashi
Molecular and Clinical Oncology.2025; 24(2): 1. CrossRef

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Gastrointestinal cancer

Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study: Xiangye Ou, Junyi Wu, Jiayi Wu, Yangkai Fu, Zhenxin Zeng, Shuqun Li, Yinan Li, Deyi Liu, Han Li, Bin Li, Jianyin Zhou, Shaowu Zhuang, Shuqun Cheng, Zhibo Zhang, Kai Wang, Shuang Qu, Maolin Yan; Cancer Res Treat. 2024;56(4):1207-1218. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1165

Abstract PDF Supplementary Material PubReader ePub

Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods
This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results
During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion
Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

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A real-world study of the efficacy of second-line treatment of unresectable hepatocellular carcinoma with esophagogastric varices after progression on first-line lenvatinib combined with PD-1 inhibitor
Saifeng Li, Qin Wen, Wenwu Huang, Zeyu Qiu, Long Feng, Fengming Yi
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Personalized prognosis in unresectable hepatocellular carcinoma: Development and validation of a model for transcatheter arterial chemoembolization plus lenvatinib
Jia-Hui Yu, Jun Yu, Jin-Xin Yu, Lin-Feng Yang, Duan Yan, Yi Liu, Ju-Rui Xian, Peng-Sheng Yi
World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef
Safety and efficacy of salvage surgery for unresectable hepatocellular carcinoma after conversion with triple therapy: a systematic review and meta-analysis of data from Chinese patients
Qingqing Pang, Xingling Mo, Zhihong Tang, Meng Wei, Danxi Liu, Zenghua Zhou, Baishan Huang, Tao Bai, Xiaobo Wang, Feixiang Wu
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Locoregional therapy combined with targeted therapy and immunotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis
Mengjie Jiang, Chao Chen, Yujie Hu, Gang Lin, Huafeng Li
Scientific Reports.2025;[Epub] CrossRef

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Lung and Thoracic cancer

Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: Insights from Real-World Data: Jeong Yun Jang, Si Yeol Song, Young Seob Shin, Ha Un Kim, Eun Kyung Choi, Sang-We Kim, Jae Cheol Lee, Dae Ho Lee, Chang-Min Choi, Shinkyo Yoon, Su Ssan Kim; Cancer Res Treat. 2024;56(3):785-794. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.1014

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.
Materials and Methods
This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).
Results
Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.
Conclusion
The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

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Efficacy and adverse events of immune checkpoint inhibitors: evidence from non-small cell lung cancer and gastric cancer in Korea and Japan
Mc Neil Valencia, Zeeshan Abbas, Seung Won Lee
Precision and Future Medicine.2025; 9(1): 15. CrossRef
Effect of interleukin-6 and interleukin-8 levels on pathogenic bacteria types in patients with advanced lung cancer and pulmonary infection during chemotherapy
Xiaodan Zheng
American Journal of Translational Research.2025; 17(6): 4723. CrossRef
Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
Hidetaka Uramoto, Nozomu Motono, Shun Iwai
Journal of Cardiothoracic Surgery.2024;[Epub] CrossRef

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Head and Neck cancer

Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn; Cancer Res Treat. 2023;55(4):1104-1112. Published online May 17, 2023; DOI: https://doi.org/10.4143/crt.2023.502

Abstract PDF Supplementary Material PubReader ePub

Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

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Abscopal Effects and Immunomodulation in Skin Cancer Therapy
William J. Nahm, Goranit Sakunchotpanit, Vinod E. Nambudiri
American Journal of Clinical Dermatology.2025; 26(4): 555. CrossRef
Proton Therapy May Reduce the Risk of Cancer Progression During Immune Checkpoint Inhibitor Therapy: A Propensity Score-Matched Analysis of Intensity Modulated Proton Versus Photon Radiation Therapy
Cong Bo, Zhenhuan Lv, Hong Zhang, Xianmin Hou, Yinxin Wang, Jing Liu, Xue Meng
International Journal of Radiation Oncology*Biology*Physics.2025;[Epub] CrossRef
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Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
Cancer Reports.2024;[Epub] CrossRef
Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
Makoto Ito, Souichiro Abe, Sou Adachi, Yukihiko Oshima, Arisa Takeuchi, Wataru Ohashi, Takashi Iwata, Tetsuya Ogawa, Akiko Ota, Yasuaki Kubota, Takahito Okuda, Kojiro Suzuki
Japanese Journal of Radiology.2024; 42(4): 424. CrossRef
Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
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Rina Jiang, Mike Fritz, Syril Keena T. Que
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Riccardo Gili, Paolo Bossi
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Gynecologic cancer

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma: Nan Kang, Yinli Zhang, Shichao Guo, Ran Chen, Fangzhou Kong, Shuchun Wang, Mingming Yuan, Rongrong Chen, Danhua Shen, Jianliu Wang; Cancer Res Treat. 2023;55(3):978-991. Published online February 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1647

Abstract PDF PubReader ePub

Purpose
The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients.
Materials and Methods
A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored.
Results
TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion.
Conclusion
This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

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Yaolin Song, Guangqi Li, Zhenqi Zhang, Yinbo Liu, Huiqing Jia, Chao Zhang, Jigang Wang, Yanjiao Hu, Fengyun Hao, Xianglan Liu, Yunxia Xie, Ding Ma, Ganghua Li, Zaixian Tai, Xiaoming Xing
Cancer Research and Treatment.2025; 57(1): 250. CrossRef
Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches
Alice Costa, Annalisa Astolfi, Livia Gozzellino, Margherita Nannini, Gianandrea Pasquinelli, Maria Abbondanza Pantaleo
Biomolecules.2025; 15(2): 265. CrossRef
Risk factors, survival analysis, and nomograms for high-grade endometrial stromal sarcoma patients with distant metastasis: a population-based study (2010–2019)
Cheng Wang, Dongni Liang, Wei Kuang, Huanxin Sun, Yuling Kou, Wei Wang, Jing Zeng
Frontiers in Oncology.2025;[Epub] CrossRef
Endometrial Stromal Sarcoma: An Update
Giulio Ricotta, Silvio Andrea Russo, Anna Fagotti, Alejandra Martinez, Elodie Gauroy, Mathilde Del, Valentin Thibaud, Bataillon Guillaume, Gwenaël Ferron
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Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights
Jan Hojný, Jiří Dvořák, Romana Vránková, Michaela Kendall Bártů, Nikola Hájková, Eva Krkavcová, Miroslava Flídrová, Ivana Stružinská, Kristýna Němejcová, Jiří Bouda, Květoslava Michalová, David Cibula, Renata Poncová, Janusz Rys, Mariusz Ksiazek, Marcin J
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Immunotherapy for high-grade endometrial stromal sarcoma: a narrative review bridging molecular insights to clinical translation
Liubiqi Zhao, Yunyi Su1, Xiaoling Li, Fang Wang, Li He, Limei Fan, Lushuang Zhang
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Lulu Feng, Lei Li, Yanmei He, Wei Jiang
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Maria Marmara, Thomas Vrekoussis, Fanourios Makrygiannakis, Dragana Nikitovic, Aikaterini Berdiaki
Cancers.2025; 17(21): 3501. CrossRef
Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival
Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai
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Yu Miao, Meng Dong, Qiyin Zhou, Julia Thiel, Na Li, Ying Cai, Dan Yuan, Haitao Wang, Su-Han Jin, Hua Yang, Jinjing Wang, Benjamin Frey, Udo S. Gaipl, Hu Ma, Jian-Guo Zhou
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Genitourinary cancer

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Hongsik Kim, Byong Chang Jeong, Joohyun Hong, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Wan Song, Hyun Hwan Sung, Jung Yong Hong, Se Hoon Park; Cancer Res Treat. 2023;55(2):636-642. Published online October 6, 2022; DOI: https://doi.org/10.4143/crt.2022.343

Abstract PDF PubReader ePub

Purpose
The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).
Materials and Methods
In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety.
Results
Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates.
Conclusion
Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

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Lingmin Kong, Bei Weng, Qian Cai, Ling Ma, Wenxin Cao, Yanling Chen, Long Qian, Yan Guo, Junxing Chen, Huanjun Wang
Academic Radiology.2025; 32(4): 2090. CrossRef
Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma
Joaquim Bellmunt, Brian M. Russell, Bernadett Szabados, Begoña P. Valderrama, Rosa Nadal
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Comparison of neoadjuvant chemotherapy and combined chemotherapy with immunotherapy for muscle-invasive bladder cancer: a propensity score-matched analysis
Hao Zhang
American Journal of Translational Research.2025; 17(1): 125. CrossRef
Improving Urothelial Carcinoma Outcomes: The Powerful Combination of Neoadjuvant and Adjuvant Chemotherapy in the Perioperative Period
Jincong Li, Yuxuan Song, Rui Chen, Hanlin Gao, Yang Liu, Yun Peng, Jilin Wu, Shicong Lai, Yiqing Du, Caipeng Qin, Tao Xu
Annals of Surgical Oncology.2025; 32(8): 6141. CrossRef
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Joseph Kattan, Clarisse Kattan, Fouad Aoun, Elie Nemr
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Ilias Giannakodimos, Afroditi Ziogou, Alexios Giannakodimos, Konstantinos Tzelepis, Zisis Kratiras, Evangelos Fragkiadis, Ioannis Zachos, Vasileios Tzortzis, Michael Chrisofos, Nikolaos Charalampakis
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Xinya Wang, Qin Zhou, Xuyan Zhang, Han Hu, Binlei Liu, Yang Wang
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Takafumi Yanagisawa, Akihiro Matsukawa, Jeremy Yuen-Chun Teoh, Keiichiro Mori, Tatsushi Kawada, Satoshi Katayama, Paweł Rajwa, Fahad Quhal, Benjamin Pradere, Marco Moschini, Shahrokh F. Shariat, Jun Miki, Takahiro Kimura
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Akihiro Matsukawa, Angelo Cormio, Marcin Miszczyk, Mehdi Kardoust Parizi, Tamás Fazekas, Ichiro Tsuboi, Stefano Mancon, Robert J. Schulz, Giulio Litterio, Ekaterina Laukhtina, Paweł Rajwa, Thomas Seisen, Keiichiro Mori, Francesca Sanguedolce, Andrea Bened
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Shugo Yajima, Naoki Imasato, Hitoshi Masuda
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Elias Antoine Karam, Yaghi César Céline, Gilles Prince, Fouad Attieh, Hampig Raphael Kourie, Joseph Kattan, Elie Nemer
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Gökhan Çolak, Bilgin Demir
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Shibo Huang, Yanping Huang, Chunyan Li, Yiwen Liang, Miaoyan Huang, Raoshan Luo, Weiming Liang
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João Queirós Coelho, Maria João Ramos, Ridhi Ranchor, Rita Pichel, Laura Guerra, Hugo Miranda, Joana Simões, Sérgio Xavier Azevedo, Joana Febra, António Araújo
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Yi Huang, Chengxiao Liao, Zefeng Shen, Yitong Zou, Weibin Xie, Qinghua Gan, Yuhui Yao, JunJiong Zheng, Jianqiu Kong
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Cheng Luo, Shuhang Luo, Wumier Wusimanjiang, Zongren Wang, Ping Liu, Bin Wang, Dan Yuan, Hao Lin, Abai Xu, Nan Deng, Kaihui Wu, Xuejin Zhu, Peng Xu, Junxing Chen, Bin Huang
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Genomic Sequencing for Bladder Urothelial Carcinoma and Its Clinical Implications for Immunotherapy: Ryul Kim, Jung Yong Hong, Jeeyun Lee, Ghee Young Kwon, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2022;54(3):894-906. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.854

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).
Materials and Methods
We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).
Results
We identified frequent molecular dysregulations in chromatin regulatory genes (KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1–positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1–negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1–positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1–positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.
Conclusion
Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.

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General

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy: Yilei Chen, Hongxing Huang, Yin Liu, Zhanghao Wang, Lili Wang, Quanxiao Wang, Yan Zhang, Hua Wang; Cancer Res Treat. 2022;54(2):362-374. Published online August 3, 2021; DOI: https://doi.org/10.4143/crt.2021.424

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells.
Materials and Methods
nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro.
Results
A high-affinity peptide (nABPD1, K_D=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (K_D=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells.
Conclusion
nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

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Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia
Quanxiao Wang, Hongxing Huang, Peisheng Liang, Lili Wang, Junheng Zheng, Yan Zhang, Hua Wang
Medical Oncology.2023;[Epub] CrossRef
Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799. CrossRef

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Sarcoma

Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression: Heejung Chae, Jeong Eun Kim, Wanlim Kim, Jong-Seok Lee, Si Yeol Song, Min Hee Lee, Hye Won Chung, Kyung-Ja Cho, Joon Seon Song, Jin-Hee Ahn; Cancer Res Treat. 2022;54(2):579-589. Published online July 6, 2021; DOI: https://doi.org/10.4143/crt.2021.496

Abstract PDF Supplementary Material PubReader ePub

Purpose
For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1).
Materials and Methods
We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS.
Results
The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes.
Conclusion
Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

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Recurrent Intrathoracic Liposarcoma: A Case Report and a Comprehensive Literature Review of a Rare Clinical Entity
Vasileios Leivaditis , Manfred Dahm , Athanasios Papatriantafyllou, Hans-Georg Keul, Lydia Kohl, Hans-Joachim Schäfers
Cureus.2024;[Epub] CrossRef
Clinicopathological Features of Intrathoracic Liposarcoma—A Systematic Review with an Illustrative Case
Kajetan Kiełbowski, Nikola Ruszel, Seweryn Adam Skrzyniarz, Małgorzata Edyta Wojtyś, Rafał Becht, Konrad Ptaszyński, Darko Gajić, Janusz Wójcik
Journal of Clinical Medicine.2022; 11(24): 7353. CrossRef

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General

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing: Hai-Yun Wang, Ling Deng, Ying-Qing Li, Xiao Zhang, Ya-Kang Long, Xu Zhang, Yan-Fen Feng, Yuan He, Tao Tang, Xin-Hua Yang, Fang Wang; Cancer Res Treat. 2021;53(4):973-982. Published online February 18, 2021; DOI: https://doi.org/10.4143/crt.2020.798

Abstract PDF Supplementary Material PubReader ePub

Purpose
Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.
Materials and Methods
TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate.
Results
The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs.
Conclusion
Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

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Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)
Qi Liu, Chunmei Zhang, Yixuan Gao, Dongmei Feng, Duo Deng, Yun Pan
Advanced Biology.2025;[Epub] CrossRef
Genome instability and crosstalk with the immune response
Roman M. Chabanon, François-Xavier Danlos, Kaissa Ouali, Sophie Postel-Vinay
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Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study
Ling Deng, Hai‐Yun Wang, Chun‐Fang Hu, Xiao‐Yun Liu, Kuntai Jiang, Juan‐Juan Yong, Xiao‐Yan Wu, Kai‐Hua Guo, Fang Wang
Pigment Cell & Melanoma Research.2024; 37(3): 363. CrossRef
Genomic Features of Homologous Recombination Deficiency in Breast Cancer: Impact on Testing and Immunotherapy
Umer Ali, Sunitha Vungarala, Venkataswarup Tiriveedhi
Genes.2024; 15(2): 162. CrossRef
Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef
Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors
Hai-Yun Wang, Ye Liu, Ling Deng, Kuntai Jiang, Xin-Hua Yang, Xiao-Yan Wu, Kai-Hua Guo, Fang Wang
Cancer Cell International.2023;[Epub] CrossRef
Homologous recombination repair gene mutations as a predictive biomarker for immunotherapy in patients with advanced melanoma
Zhixuan You, Meng Lv, Xuanyu He, Yingqin Pan, Junfeng Ge, Xue Hu, Yating Zheng, Mengli Huang, Chengzhi Zhou, Changxuan You
Frontiers in Immunology.2022;[Epub] CrossRef
The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy
Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies
P. Sean Walsh, Yangyang Hao, Jie Ding, Jianghan Qu, Jonathan Wilde, Ruochen Jiang, Richard T. Kloos, Jing Huang, Giulia C. Kennedy
Journal of Personalized Medicine.2022; 13(1): 24. CrossRef

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Clinical Outcomes of Immune Checkpoint Blocker Therapy for Malignant Melanoma in Korean Patients: Potential Clinical Implications for a Combination Strategy Involving Radiotherapy: Jeongshim Lee, Jee Suk Chang, Mi Ryung Roh, Minkyu Jung, Choong-Kun Lee, Byung Ho Oh, Kee Yang Chung, Woong Sub Koom, Sang Joon Shin; Cancer Res Treat. 2020;52(3):730-738. Published online February 13, 2020; DOI: https://doi.org/10.4143/crt.2019.598

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT).
Materials and Methods
We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR).
Results
The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders.
Conclusion
ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).

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Japanese Dermatological Association Guidelines: Clinical Questions of Guidelines for Melanoma 2025
Satoshi Fukushima, Takamichi Ito, Jun Asai, Hiroshi Igaki, Ryota Tanaka, Kenjiro Namikawa, Ayato Hayashi, Akane Minagawa, Takuya Miyagawa, Azusa Miyashita, Dai Ogata, Mao Okumura, Yukiko Kiniwa, Hiroyuki Goto, Takeshi Namiki, Hiroki Hashimoto, Tokimasa Hi
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Ielizaveta Gorodetska, Alexander Schulz, Gerhard Behre, Anna Dubrovska
Cancers.2025; 17(16): 2648. CrossRef
Inhibiting Fatty Acid Oxidation Suppresses Acquired Resistance to Standard Chemotherapy in Melanoma
Wonyoung Choi, Woojin Ham, Jeong Hwan Park, Sung Hoon Sim, Jung Won Chun, Mingyu Kang, Chaeyoung Kim, Woosol Hong, Eun-Byeol Koh, Joon Hee Kang, Sang Myung Woo, Soo-Youl Kim
International Journal of Molecular Sciences.2025; 26(20): 9873. CrossRef
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Harpreet Kaur, Bishmita Gogoi, Ira Sharma, Deepak Kumar Das, Mohd Ashif Azad, Devlina Das Pramanik, Arindam Pramanik
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Neda Mohaghegh, Amir Ahari, Fatemeh Zehtabi, Claire Buttles, Saya Davani, Hanna Hoang, Kaylee Tseng, Benjamin Zamanian, Safoora Khosravi, Ariella Daniali, Negar Hosseinzadeh Kouchehbaghi, Isabel Thomas, Hamed Serati Nouri, Danial Khorsandi, Reza Abbasghol
Acta Biomaterialia.2023; 172: 67. CrossRef
Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis
Gaofei Yin, Wei Guo, Zhigang Huang, Xiaohong Chen
Melanoma Research.2022; 32(2): 71. CrossRef
The pharmacotherapeutic management of nail unit and acral melanomas
Julianne M. Falotico, Shari R. Lipner
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Jina Kim, Jee Suk Chang, Wonmo Sung, Jin Sung Kim, Tae Hyung Kim, Seo Hee Choi, Kyung Hwan Kim, Heejoo Ko, Hye Sun Lee, Soyoung Jeon, Sang Joon Shin, Mitchell Liu, Robert Olson
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Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators
Hwa Kyung Byun, Jee Suk Chang, Minkyu Jung, Woong Sub Koom, Kee Yang Chung, Byung Ho Oh, Mi Ryung Roh, Kyung Hwan Kim, Choong-Kun Lee, Sang Joon Shin
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Jennifer Ben Shimol, Yuli Guzman-Prado, Maria Karlinskaya, Tima Davidson
Critical Reviews in Oncology/Hematology.2021; 167: 103499. CrossRef

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Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response: Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-hong Park, Seung-Mo Hong, Kyu-pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo; Cancer Res Treat. 2020;52(2):594-603. Published online December 18, 2019; DOI: https://doi.org/10.4143/crt.2019.493

Abstract PDF PubReader ePub

Purpose
The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.
Materials and Methods
In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.
Results
Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).
Conclusion
Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

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Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects: Chul Won Choi, Min Ho Jeong, You-Soo Park, Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh; Cancer Res Treat. 2019;51(2):464-473. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2018.186

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs).
Methods
and Materials CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system.
Results
Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group.
Conclusion
The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.

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Case Report

Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report: Haa-Na Song, Min Gyu Kang, Jeong Rang Park, Jin-Yong Hwang, Jung Hun Kang, Won Seop Lee, Gyeong-Won Lee; Cancer Res Treat. 2018;50(4):1458-1461. Published online January 22, 2018; DOI: https://doi.org/10.4143/crt.2017.529

Abstract PDF PubReader ePub

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

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Original Articles

Ipilimumab Real-World Efficacy and Safety in Korean Melanoma Patients from the Korean Named-Patient Program Cohort: Minkyu Jung, Jeeyun Lee, Tae Min Kim, Dae Ho Lee, Jin Hyung Kang, Sung Young Oh, Soo Jung Lee, Sang Joon Shin; Cancer Res Treat. 2017;49(1):44-53. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.024

Abstract PDF PubReader ePub

Purpose
Ipilimumab improves survival in advanced melanoma patients. However, the efficacy and safety of ipilimumab has not been evaluated in Asian melanoma patients with a high frequency of mucosal and acral melanoma subtypes.
Materials and Methods
Advanced melanoma patients treated with 3 mg/kg ipilimumab in a Korean multicenter named-patient program (NPP) were evaluated between September 2014 and July 2015. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes.
Results
A total of 104 advanced melanoma patients were treated. The primary sites were acral (31.7%), mucosal (26%), cutaneous (26%), uveal (9.6%), and unknown (6.7%). Sixty-eight patients (65.4%) experienced adverse events, and the most common toxicity was skin rash (22.1%), 10 patients (9.6%) experienced adverse events of grade 3 or higher. The median progression-free survival (PFS) was 2.73 months (95% confidence interval, 2.67 to 2.85), and there was no difference in PFS according to subtypes. Poor performance status, liver metastasis, and NLR (≥5) were independent poor prognostic factors by multivariate analysis.
Conclusion
In the Korean NPP cohort, ipilimumab showed similar efficacy and tolerability compared to Western patients, regardless of subtypes. All subtypes should benefit from ipilimumab with consideration of performance status, liver metastasis, and NLR.

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Improved Efficacy of a Dendritic Cell-Based Vaccine against a Murine Model of Colon Cancer: The Helper Protein Effect: Amir-Hassan Zarnani, Monireh Torabi-Rahvar, Mahmood Bozorgmehr, Mehri Zareie, Nazanin Mojtabavi; Cancer Res Treat. 2015;47(3):518-526. Published online November 27, 2014; DOI: https://doi.org/10.4143/crt.2013.241

Abstract PDF PubReader ePub

Purpose
Targeted immunotherapy using dendritic cells (DCs) has been employed in numerous investigations aiming at combating neoplasms. We previously showed that copulsing of an antigen with a helper protein could considerably enhance antigen presenting capacity of ex vivo–generated DCs. In this study, we attempted to administer an effective treatment in a murine model of colon cancer with DCs pulsed with the mixture of a tumor-specific gp70-derived peptide (AH1) and a helper protein, ovalbumin (OVA). Materials and Methods First, the presence of gp70 in CT26 tumor cells and tumor tissues was verified using immunofluorescence and Western blot analyses. Next, DCs were purified from normal mice, loaded ex vivowith AH1 and OVA (DC-Pep-OVA), and injected into tumor-bearing mice. Tumor volume, in vitro antigen (Ag)-specific proliferation of splenic cells, and survival rate were measured to determine the efficacy of DC-Pep-OVA. As the control groups, tumor-bearing mice were vaccinated with DC-Pep, unpulsed DC, and DCs loaded with a mixture of OVA and an irrelevant peptide (P15), or were not vaccinated at all. Results DC-Pep-OVA showed superior efficacy over other groups, as indicated by smaller tumor volume, higher Ag-specific proliferation rate of splenic cells, and prolonged survival. Conclusion Overall, in the present study we showed for the first time that DCs copulsed with AH1 (tumor Ag) and OVA (helper molecule) could be considered as potentially robust weapons for use in future antitumor immunotherapies.

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Antitumor Effects of DC Vaccine With ALA-PDT-Induced Immunogenic Apoptotic Cells for Skin Squamous Cell Carcinoma in Mice
Haiyan Zhang, Peiru Wang, Xiaojie Wang, Lei Shi, Zhixia Fan, Guolong Zhang, Degang Yang, Cody F. Bahavar, Feifan Zhou, Wei R. Chen, Xiuli Wang
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O. V. Markov, N. L. Mironova, E. V. Shmendel, M. A. Maslov, M. A. Zenkova
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A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment
Ko-Jiunn Liu, Tsu-Yi Chao, Jang-Yang Chang, Ann-Lii Cheng, Hui-Ju Ch’ang, Woei-Yau Kao, Yu-Chen Wu, Wei-Lan Yu, Tsai-Rong Chung, Jacqueline Whang-Peng
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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.

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Julián A. Chamucero-Millares, David A. Bernal-Estévez, Carlos A. Parra-López
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Charles Shin, Sung Soo Kim, Yong Hwa Jo
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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
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The Effect of Immunotherapy Based on Interferon - alpha in Advanced Renal Cell Carcinoma: Seung Hyun Jeon, Sung Goo Chang; J Korean Cancer Assoc. 1999;31(5):986-994.

Abstract PDF: PURPOSE
Recently in light of the development in immunology, interferon- e and inter- leukin-2 or combination therapy with anticancer drugs have been performed. This study aims to verify and compare the efficacy of therapies using interferon- a alone, interferon- a plus vinblastine, and interferon- a plus interleukin-2 plus 5-fluorouracil (5-FU) plus 13-cis retinoic acid (13cRA) in patients with advanced renal cell carcinoma.
MATERIALS AND METHODS
A total of 29 patients were randomly assigned to receive treatment with either interferon- a alone or interferon- a plus vinblastine or interferon- a plus interleukin-2 plus 5-FU plus 13cRA from December 1989 to May 1998. The most frequent metastatic sites were the lung, lymph nodes, bone, liver, and brain. We studied the response rates, survival period, and complications of each regimen.
RESULTS
Responses were achieved in 1 out of 1~5 patients (6.73?o) on interferon- a alone (partial responses lasting 13 months), 1 out of 9 patients (11.1%) on interferon- e plus vinblastine (partial responses lasting 25 months) and 1 out of 5 patients (20.0%) on interferon-a plus IL-2 plus 5-FU plus 13cRA regimen (partial responses lasting 14 months). The median durations of survival were 18, 33, and 23 months respectively. The overall response rate was 10.3% and overall median duration of survival was 19 months. The most common side effects were flu-like symptom such as fever, chills (93.1%), skin symptom such as erythema, pruritus (31.0%), G-I symptom such as nausea, vomiting (17.2%), netropenia (10.3%), abnormal LFT (10.3%), and thrombocytopenia (3.4%).
CONCLUSIONS
This study confirms the manageability and tolerability of several regimen used. There is no significant differences in response rates and survival duration among the regimens used in this study. The effective immunotherapy in patients with metastatic RCC should be evaluated by further studies of larger patients groups even though a minority of patients responded.

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Immunoregulatory Effect of Mesima (R) as an Immunotherapeutic Agent in Stage III Gastric Cancer Patients after Radical Gastrectomy: Jin Pok Kim, Keon Young Lee, Hang Jong Yu, Han Kwang Yang; J Korean Cancer Assoc. 1997;29(3):383-390.

Abstract PDF: PURPOSE
The effectiveness of adjuvant immunotherapy with Mesima (R) in advanced adenocarcinoma of the stomach was evaluated.
MATERIALS AND METHODS
45 patients with stage III gastric cancer after radical gastrectomy were divided into three groups at random. The first group received Mesima. The second group received OK-432 and the third group received no immunotherapeutic agent at all. All three groups received adjuvant chemotherapy using 5-FU and mitomycin-C protocol. The numbers of total T lymphocytes were checked along with the T4 and T8 subpopulation and B lymphocytes and natural killer (NK) cells preoperatively and 9 days, 3 months and 7 months postoperatively. The delayed-type cutaneous hypersensitivity were also checked preoperatively and 3 months and 7months postoperatively.
RESULTS
All three groups showed initial decrease in the total T lymphocyte count and T4 lymphocyte count at 9 days postoperatively, which showed gradual increase over the 7 months postoperative period. The Mesima (R)-treated group and OK-432-treated group showed significantly better recovery rate at 7 months postoperatively than the control group. The number of T8 lymphocytes and NK cells also showed initial decrease and later recovery, but there was no significant difference between groups. The number of B lymphocytes showed gradual decrease over 7 months in the Mesima (R)-treated group and the control group, and initial decrease with later increase in the OK-432-treated group, again with no significant difference. The average numbers of positive antigens on delayed cutaneous hypersensitivity test were decreased initially with gradual increase, but there was no significant difference between groups.
CONCLUSION
Mesima (R) can be considered as a candidate for safe and effective immunotherapeutic agent in patients with gastric cancer, but the actual benefit in increasing patient survival should be determined through a long term follow-up study.

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