Cancer immunology, immunotherapy : CII最新文献

{"title":"Vorinostat unmasks MAEL to enhance DC vaccine-induced CTL killing in hepatocellular carcinoma, potentiated by TIGIT checkpoint inhibition.","authors":"Can Liu, Qianru Zhang, Jingjing Zhang, Wenpeng Liu, Shengya Geng, Jiandong Zhang","doi":"10.1007/s00262-026-04410-2","DOIUrl":"10.1007/s00262-026-04410-2","url":null,"abstract":"<p><strong>Background: </strong>To address the limited immunogenicity and immune evasion in hepatocellular carcinoma (HCC), this study developed a combinatorial immunotherapy strategy combining antigen-specific vaccination, epigenetic modulation, and TIGIT-targeted checkpoint blockade.</p><p><strong>Methods: </strong>Bioinformatic screening identified the cancer-testis antigen MAEL as a target. HLA-A*02:01-restricted MAEL peptides were used to pulse monocyte-derived dendritic cells (DCs), which primed cytotoxic T lymphocytes (CTLs). The CTL cytotoxicity against HCC cells was tested. HCC cells were treated with the HDAC inhibitor vorinostat to enhance MAEL expression, and its impact on CTL killing was evaluated. The triple combination (MAEL specific CTLs + vorinostat + anti-TIGIT) was tested in HCC xenograft mouse models, with analyses of tumor growth, survival, and immune infiltration.</p><p><strong>Results: </strong>MAEL was confirmed as an HCC-associated antigen with restricted normal tissue expression. MAEL peptide-pulsed DCs generated potent CTLs with cytotoxicity against HLA-A*02:01⁺ HCC lines. Vorinostat upregulated MAEL expression, enhancing CTL killing (p < 0.01). In vivo, the dual combination (MAEL specific CTLs + vorinostat) outperformed monotherapies, reducing tumor growth and prolonging survival. The triple combination achieved the strongest anti-tumor effects, with significant regression and extended survival, via increased activated MAEL specific CD8⁺ T cell infiltration and enhanced CTL effector functions (elevated IFN-γ, TNF-α).</p><p><strong>Conclusion: </strong>This triple combination strategy synergistically enhances HCC immunotherapy. Vorinostat induces MAEL expression to \"unmask\" tumors, while TIGIT blockade overcomes T cell exhaustion, amplifying antigen-specific CTL activity. This approach shows promise for HCC treatment.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early increase of CD103 expression on peripheral PD-1⁺ CD8⁺ T cells predicts response to nivolumab in advanced esophageal squamous cell carcinoma.","authors":"Satoko Sumimoto, Tomoki Makino, Shigeto Nakai, Takaomi Hagi, Kota Momose, Kotaro Yamashita, Takuro Saito, Koji Tanaka, Tsuyoshi Takahashi, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1007/s00262-026-04429-5","DOIUrl":"10.1007/s00262-026-04429-5","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab has become a standard treatment for advanced or recurrent esophageal squamous cell carcinoma (ESCC). However, reliable blood-based biomarkers predictive of response remain undefined. We investigated dynamic changes in peripheral PD-1⁺ CD8⁺ T-cell subsets during nivolumab therapy and evaluated their clinical significance.</p><p><strong>Patients and methods: </strong>Fifty-seven patients with advanced or recurrent ESCC treated with nivolumab were enrolled in this retrospective observational study. Peripheral blood mononuclear cells were collected before treatment and at 1, 2, and 4 weeks after initiation. Flow cytometric analyses evaluated the expression of CD103, CD45RA, Tim-3, LAG-3, TIGIT, and Ki-67 among nivolumab-binding PD-1⁺CD8⁺ T cells. Associations between immunophenotypic changes, treatment response, survival outcomes, immune-related adverse events (irAEs), and nutritional/inflammatory indices were analyzed.</p><p><strong>Results: </strong>The objective response rate was 24.6%, and the median overall survival (OS) was 11.7 months. CD103 expression among PD-1⁺ CD8⁺ T cells significantly increased after nivolumab initiation and was sustained up to 4 weeks. At 4 weeks, responders showed significantly higher CD103 frequency than non-responders (P = 0.00407). Patients with high CD103 expression demonstrated significantly improved OS (P = 0.0421), whereas progression-free survival was not significantly different. CD103 expression was not correlated with baseline nutritional or inflammatory markers. Responders more frequently experienced irAEs, particularly rash.</p><p><strong>Conclusions: </strong>Early elevation of CD103 expression among peripheral PD-1⁺ CD8⁺ T cells was associated with objective response and improved overall survival in patients with ESCC and may represent a minimally invasive exploratory biomarker during nivolumab therapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding circulating neutrophil phenotypes in triple-negative breast cancer via optimized single-cell RNA sequencing.","authors":"Marcin Banacki, Krzysztof Pastuszak, Michał Sieczyński, Grażyna Suchodolska, Elżbieta Senkus, Iwona Inkielewicz-Stepniak, Anna Supernat, Anna Żaczek","doi":"10.1007/s00262-026-04345-8","DOIUrl":"10.1007/s00262-026-04345-8","url":null,"abstract":"<p><p>Neutrophils are emerging as key regulators of tumor biology, influencing cancer progression, immune evasion, and therapeutic response. However, their transcriptomic characterization remains challenging due to low RNA content, limiting confident discrimination from other leukocyte populations at the single-cell level. To address this, we developed a robust analytical framework for single-cell RNA sequencing data, calculating a neutrophil score for each cell based on two curated neutrophil marker gene panels and excluding cells expressing non-neutrophil marker genes.White blood cells were isolated from liquid biopsies of six triple-negative breast cancer (TNBC) patients and six non-malignant donors, sequenced, and analyzed to profile 84 neutrophils isolated from TNBC patients and 128 neutrophils isolated from control donors. TNBC neutrophils displayed significant upregulation of migration-associated genes (-log₁₀ adjusted p ≈ 3) and respiratory complex genes (p < 1 × 10^-9) compared with controls.These findings demonstrate significant transcriptomic differences between the TNBC and control neutrophils, revealing a part of the influence of the TNBC tumor on circulating immune cells. Moreover, this work provides a validated framework for precise neutrophil identification and functional characterization in single-cell studies and lays the foundation for dissecting their mechanistic roles in cancer progression.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Metabolic syndrome and immune-related adverse events.","authors":"Katherine Lei, Meera J Patel, Jialiang Liu, Rutu Aniruddha Rathod, Mitchell S von Itzstein, Farjana J Fattah, Hong Mu-Mosley, Jeffrey A SoRelle, Jason Y Park, Yang Xie, Amy E Hughes, Heather Kitzman, David E Gerber","doi":"10.1007/s00262-026-04402-2","DOIUrl":"10.1007/s00262-026-04402-2","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NY-ESO-1 and PD-L1 as biomarkers associated with nivolumab response and outcome in unresectable or recurrent esophageal squamous cell carcinoma: a multicenter biomarker study.","authors":"Shigeto Nakai, Tomoki Makino, Kota Momose, Kotaro Yamashita, Koji Tanaka, Hiroshi Miyata, Sachiko Yamamoto, Masaaki Motoori, Yutaka Kimura, Tomohira Takeoka, Motohiro Hirao, Jin Matsuyama, Yusuke Akamaru, Yukinori Kurokawa, Eiichi Morii, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1007/s00262-026-04415-x","DOIUrl":"10.1007/s00262-026-04415-x","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death protein-1 (PD-1) blockade improves survival in esophageal squamous cell carcinoma (ESCC), although only a subset of patients respond. We aimed to identify tumor-related biomarkers associated with response and outcome in patients with unresectable or recurrent ESCC.</p><p><strong>Methods: </strong>This multicenter retrospective study included 250 patients with unresectable or recurrent ESCC who received nivolumab as second- or later-line therapy. Pretreatment tumor specimens were evaluated by immunohistochemistry for p53, NY-ESO-1, MLH1, and programmed death-ligand 1 (PD-L1). PD-L1 expression was assessed using both tumor proportion score (TPS) and combined positive score (CPS) by using automated digital image analysis. Associations with objective response, progression-free survival (PFS), and overall survival (OS) were analyzed.</p><p><strong>Results: </strong>NY-ESO-1 expression was significantly associated with response to nivolumab (28.6% vs. 11.1%, P = 0.005) and remained independently associated with response in multivariate analysis (OR 3.32, 95% CI 1.49-7.28, P = 0.0027). PD-L1 expression was also associated with response according to both CPS and TPS. Patients with CPS ≥ 10% showed higher response rates than those with CPS < 10% (24.1% vs. 10.2%, P = 0.003), as well as longer median PFS (2.6 vs. 2.0 months, P = 0.0173) and OS (12.3 vs. 10.4 months, P = 0.0479). In contrast, p53 expression showed no significant association with response or survival, and MLH1 loss was rare.</p><p><strong>Conclusions: </strong>NY-ESO-1 expression was associated with response to nivolumab, while PD-L1 expression, particularly CPS, may provide clinically relevant prognostic information. Integrated assessment of tumor-related biomarkers and the host immune microenvironment may further improve patient stratification in ESCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal variation in immune-related adverse events in advanced cancer patients.","authors":"Roger Liang, Bo Gao, Adnan Nagrial, Tania Moujaber, Matteo S Carlino, Pei N Ding, Howard Gurney, Mark Wong, Rosemary Habib, Serigne N Lo, Janet McKeown, Ines Pires da Silva","doi":"10.1007/s00262-026-04423-x","DOIUrl":"10.1007/s00262-026-04423-x","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) improve outcomes across advanced cancers but can cause immune-related adverse events (irAEs). Seasonal environmental factors influence immune regulation and autoimmunity, yet its relationship with irAE development in non-melanoma cancers remains poorly defined.</p><p><strong>Methods: </strong>We retrospectively analysed patients with advanced non-melanoma solid tumours treated with anti-PD-1/PD-L1 and/or anti-CTLA-4 monotherapy at two Australian tertiary centers between 2014-2024. Seasonal variation in irAE incidence, organ distribution, severity, and timing were evaluated using descriptive analyses, Kaplan-Meier estimates and Cox proportional hazards models.</p><p><strong>Results: </strong>Among 709 patients across 27 cancer types (median follow-up 12.7 months), 514 irAEs occurred, including 32% grade ≥ 3 events and 14% treatment discontinuation rate due to toxicity. Winter ICI initiation led to the highest irAE rate (0.89 events per treatment) versus summer (0.62), largely driven by seasonal variation in low-grade cutaneous and thyroid events. Summer ICI initiation showed the highest proportion of grade ≥ 3 irAEs, whereas winter had the lowest. Seasonal effects also differed by regimen intensity, with disproportionately more irAEs among patients commencing doublet ICIs in winter. Season of ICI initiation was not significantly associated with overall irAE risk (p = 0.174) or time to onset (p = 0.11). However, time to first irAE differed by season of toxicity onset (p = 0.019), with earlier irAEs occurring in spring and summer.</p><p><strong>Conclusions: </strong>Although there was no significant association between season of ICI initiation and overall irAE risk, we observed seasonal variations in the phenotype, severity, and timing of irAEs. These exploratory findings may inform future investigation into seasonal influences on immune toxicity.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broader gene representation by whole-exome sequencing improves accuracy of tumor mutational burden assessment for selection of pembrolizumab immunotherapy.","authors":"Milan Radovich, James Wacker, Jeffrey Solzak, Hongseok Tae, Jennifer R Ribeiro, Todd Maney, Bradley Hancock, James Hamrick, George W Sledge, Manmeet S Ahluwalia, Stephen V Liu, Emil Lou, Vivek Subbiah, Balazs Halmos, Daniel Magee, David B Spetzler","doi":"10.1007/s00262-026-04365-4","DOIUrl":"10.1007/s00262-026-04365-4","url":null,"abstract":"<p><p>Although the tissue-agnostic FDA approval of pembrolizumab for tumor mutational burden (TMB)-high tumors has provided meaningful clinical benefit to patients, there remains a need to optimize TMB assessment. In this cohort study, we investigated the discordance between whole-exome sequencing (WES) and panel-based methods and evaluated their relative clinical utility in identifying patients likely to benefit from pembrolizumab. Molecularly-profiled tumors from patients treated with pembrolizumab were analyzed (N = 26,756). TMB was calculated using WES data or panels of genes (324, 523, and 648) from commercially available assays (TMB-High ≥ 10 mutations/Mb). Pembrolizumab-specific overall survival (OS) was calculated from insurance claims data (treatment start to last contact). Targeted gene panels tended to overestimate TMB and demonstrated ~ 10-15% discordance in binary TMB calls from WES, which was most pronounced for the smallest panel. Discordant cases for all three panels clustered near the TMB clinical calling threshold. WES offered improved stratification of patients for pembrolizumab treatment: in a subset of \"TMB-reliant\" tumor types lacking disease-specific immune checkpoint inhibitor (ICI) indications (n = 3,981), median OS was approximately 5 months longer for cases identified as WES-TMB-High but panel-TMB-Low compared to those identified as WES-TMB-Low but panel-TMB-High (p < 0.05 for 324-gene and 648-gene panels). Approximately, 10-11% of patients were potentially misclassified by panels. These findings emphasize the importance of broader gene representation for accurate TMB determination near the clinical threshold-especially in tumor types lacking disease-specific ICI indications, where tissue-agnostic MSI-High/dMMR or TMB-High labeling represents the principal on-label route to ICI therapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical preconditioning by shear stress enhances memory formation and anti-tumor function of CAR-T cells.","authors":"Lianfeng Zhao, Jiaqi Liu, Yan Zhang, Xinhao Yang, Tianyu Chen, Xinyang Xu, Muya Zhou, Zhigang Hu, Zhigang Guo","doi":"10.1007/s00262-026-04391-2","DOIUrl":"10.1007/s00262-026-04391-2","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable success in the treatment of hematological malignancies, and its application to solid tumors is currently under active investigation. Upon infusion into the bloodstream, CAR-T cells are exposed to fluid shear stress (SS) generated by blood flow. However, the impacts of SS on CAR-T cells function are not well understood. In this study, we exposed anti-mesothelin (MSLN) CAR-T cells to a shear stress of 5 dynes/cm2, and observed reduced cell viability, enhanced activation, and decreased expression of exhaustion markers. Notably, we found that a one-hour SS stimulation applied seven days after T cell isolation and activation significantly increased the proportion of stem cell memory T cells (Tscm), mitigated exhaustion, and enhanced the anti-tumor efficacy of anti-MSLN CAR-T cells. Furthermore, SS-preconditioned CAR-T cells exhibited resistance to SS-induced cell death and demonstrated increased migratory capacity. In vivo experiments, SS-preconditioned CAR-T cells exhibited greater tumor infiltration, improved persistence, superior tumor control, and a favorable safety profile in tumor-bearing mice. Transcriptomic analysis revealed upregulation of genes associated with activation, infiltration, and microtubule dynamics, alongside downregulation of genes linked to exhaustion, apoptosis, and immunosuppression. Collectively, our findings demonstrate for the first time that mechanical preconditioning with fluid shear stress can reprogram CAR-T cells toward a more functional and persistent phenotype, offering a novel strategy to optimize CAR-T therapy for solid tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabozantinib and atezolizumab for recurrent or metastatic esophageal squamous cell carcinoma after platinum-based chemotherapy failure: a single-arm phase II study and biomarker analysis.","authors":"Hung-Yang Kuo, Ta-Chen Huang, Chien-Huai Chuang, Tsung-Che Wu, Yen-Lin Huang, Chia-Chi Lin, Jang-Ming Lee, Jhe-Cyuan Guo, Chih-Hung Hsu","doi":"10.1007/s00262-026-04408-w","DOIUrl":"10.1007/s00262-026-04408-w","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-PD-1 immune-checkpoint inhibitors (ICIs) are approved for treating patients with recurrent or metastatic (R/M) esophageal squamous cell carcinoma (ESCC) who have failed platinum-based chemotherapy. However, their efficacy as monotherapy remains limited. We hypothesized that adding cabozantinib, a multikinase inhibitor with antiangiogenic and immunomodulatory properties, could enhance the therapeutic efficacy of atezolizumab, an anti-PD-L1 ICI, in patients with R/M ESCC.</p><p><strong>Patients and methods: </strong>A single-arm, single-institution phase II trial was conducted (NCT05007613) that included patients with ESCC who experienced disease progression following a platinum-based chemotherapy for R/M ESCC or within 6 months after chemo(radio)therapy for locoregional disease. Participants received cabozantinib 40 mg daily and atezolizumab 1200 mg every 3 weeks until disease progression or intolerable toxicity was reached. The primary endpoint was investigator-assessed objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile.</p><p><strong>Results: </strong>Between June 2021 and March 2024, 24 patients were enrolled in this study. With a median follow-up of 7.0 months (range, 0.5-38.1), 7 patients achieved partial responses and 7 had stable disease. The ORR was 29.1% (95% CI = 11.7%-60.1%), and the disease control rate (DCR) was 58.3% (95% CI = 31.9-97.9%). The median duration of response was 6.5 months (95% CI = 0.9-12.1), the median PFS was 2.2 months (95% CI = 0.64-3.76), and the median OS was 7 months (95% CI = 2.36-11.64). Of the 24 patients, 12 (50%) experienced ≥ grade 3 treatment-related adverse events. Patients with high PD-L1 expression and increased intratumoral or stromal CD8+ tumor infiltrating lymphocytes had numerically higher ORR and improved OS.</p><p><strong>Conclusion: </strong>The combination of cabozantinib and atezolizumab has an acceptable safety profile and moderate antitumor activity as a second-line treatment for patients with R/M ESCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel recombinant protein PK5-Gal-3C enhances the anti-tumor activity of T cells via binding with TRPV2.","authors":"Guopeng Zhang, Wei Zhang, Xiaohuan Wei, Zhenyu Wang, Feitong Wang, Shishuo Sun, Haiheng Xu, Xiangye Liu, Qing Zhang, Xiaoge Gao","doi":"10.1007/s00262-026-04401-3","DOIUrl":"10.1007/s00262-026-04401-3","url":null,"abstract":"<p><p>Investigating strategies to enhance T cell effector function can improve the adoptive immune responses to tumors and complement existing tumor immunotherapies. Here, we present a novel artificially designed recombinant protein, PK5-Gal-3C, which is composed of the fifth kringle domain of plasminogen (PK5) and the C-terminal carbohydrate-recognition domain of galectin-3 (Gal-3C). This protein exhibited potent anti-tumor activity by significantly enhancing T cell effector function. Specifically, PK5-Gal-3C directly activated T cells by binding to glycosylated TRPV2 via Gal-3C, a thermosensitive calcium-permeable cation channel, thereby promoting the influx of calcium ions to enhance T cells cytotoxicity via the activation of c-Jun. Correspondingly, inhibition of TRPV2 or c-Jun impaired the cytotoxicity of T cell mediated by PK5-Gal-3C. Additionally, PK5-Gal-3C demonstrated significant anti-tumor activity by enhancing T cell tumor infiltration and cytotoxicity in a mouse model, as well as improving the anti-tumor efficacy of CAR-T cells in solid tumors. In summary, PK5-Gal-3C is a safe and potent anti-tumor agent with promising potential for T cell-mediated cancer immunotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}