Cancer immunology, immunotherapy : CII最新文献

{"title":"GFI1 enhances MHC-I expression in tumor cells and augments tumor responsiveness to PD-1/PD-L1 inhibitors.","authors":"Yu Xi, Kewei Xiao, Kelin Meng, Taiyan Yu, Tianlai Wang, Xu Wang, Ounan Pan, Chenxi Zeng, Xue Wang, Xiangning Fu, Lequn Li","doi":"10.1007/s00262-026-04430-y","DOIUrl":"10.1007/s00262-026-04430-y","url":null,"abstract":"<p><strong>Background: </strong>Growth factor-independent-1 transcription repressor (GFI1) is crucial for determining the differentiation and fate of exhausted CD8⁺ T cells and affects immunotherapy outcomes. However, the effects of tumor cell-intrinsic GFI1 on antitumor immunity and the response to immunotherapy remain unknown.</p><p><strong>Methods: </strong>The tumor cell-intrinsic expression of GFI1 was examined via RT‒qPCR and Western blotting. Immunohistochemical staining of tumor tissues was performed to assess the relationships among GFI1, CD8, and MHC I expression. A syngeneic mouse model and clinical tumor samples from NSCLC patients undergoing immunochemotherapy were used to evaluate how tumor cell-intrinsic GFI1 affects the response to immunotherapy. Additionally, techniques such as flow cytometry, immunoprecipitation, ChIP-qPCR, immunofluorescence, and both loss- and gain-of-function approaches were employed to investigate the underlying mechanisms involved.</p><p><strong>Results: </strong>Tumor-intrinsic GFI1 expression was positively associated with MHC I expression and the infiltration of CD8⁺ T cells. Tumors with higher GFI1 levels showed a significantly better response to immunotherapy. The overexpression of GFI1 in tumor cells increases MHC-I expression in a STAT1-dependent manner. Mechanistic analysis revealed that GFI1 inhibits HDAC1 activity in tumor cells by promoting its export to the cytoplasm, thereby increasing H3K9 acetylation and the transcription of STAT1 and MHC-I. Additionally, phenformin, an AMPK activator, increases GFI1 levels by downregulating EZH2 expression. Compared with anti-PD-L1 therapy alone, combining phenformin with anti-PD-L1 therapy enhances antitumor effects.</p><p><strong>Conclusions: </strong>This study demonstrated the crucial role of tumor-intrinsic GFI1 in enhancing antitumor immune responses, suggesting a new target for increasing the effectiveness of PD-1/PD-L1 blockade.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008352","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":"Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells.","authors":"Van-Tan Nguyen, Thuy Nguyen Thi, Van-Dinh-Huan Tran, Manh-Cuong Vo, Tan-Huy Chu, Ho Cheol Jang, Mihee Kim, Ga-Young Song, Seo-Yeon Ahn, Jae-Sook Ahn, Deok-Hwan Yang, Hyeoung-Joon Kim, Duck Cho, Changho Lee, Sung-Hoon Jung, Je-Jung Lee","doi":"10.1007/s00262-026-04418-8","DOIUrl":"10.1007/s00262-026-04418-8","url":null,"abstract":"<p><p>CD44 is a cell-surface glycoprotein frequently overexpressed in cancers and associated with poor prognosis. We evaluated the prognostic significance of CD44 overexpression in multiple myeloma (MM) and investigated the therapeutic efficacy of combining natural killer (NK) cell therapy with all-trans retinoic acid (ATRA) and bortezomib (Bor) against CD44-overexpressing MM. Clinical data from the CoMMpass database were analyzed to assess survival outcomes relative to CD44 expression. NK cells were expanded from healthy donors using K562-OX40L-mbIL-18/21 feeder cells supplemented with interleukin (IL)-2 and IL-15. Functional assays were performed using CD44-high myeloma cell lines treated with ATRA and Bor, individually or in combination with NK cells. Therapeutic efficacy was evaluated based on tumor growth, systemic dissemination, and survival in an intravenous U266-green fluorescent protein-firefly luciferase xenograft NOD/SCID IL-2Rγnull mouse model. Clinical data showed CD44 overexpression correlated with inferior overall survival (P < 0.0001) in all three stages I, II, and III of the revised International Stage System. In vitro, ATRA and Bor co-treatment downregulated β-catenin and CD44 expression, inhibited proliferation, migration, and invasion, and enhanced NK cell-mediated cytotoxicity via upregulation of MICA/B, Fas, TRAIL-R2, and intercellular adhesion molecule-1. In vivo, combination therapy with NK cells, ATRA, and Bor significantly suppressed CD44 expression, reduced extramedullary spread, and prolonged survival without notable toxicity. These preclinical findings support CD44 overexpression as a marker associated with inferior survival in MM and provide a rationale for pharmacologic tumor priming with ATRA and bortezomib to enhance NK cell-mediated cytotoxicity. However, the therapeutic strategy requires further validation in heterogeneous patient-derived models and prospective clinical studies before clinical efficacy can be inferred.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985009","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":"Cytokine-induced killer (CIK) Cells-associated transcriptome signature reveals the potential immunomodulatory role of TNFSF14 in clear cell renal cell carcinoma.","authors":"Yinhao Chen, Linli Chen, Xinyue Qin, Yutao Li, Di Wu, Maria Fitria Setiawan, Veronika Lukacs-Kornek, Manuel Ritter, Amit Sharma, Ingo G H Schmidt-Wolf","doi":"10.1007/s00262-026-04422-y","DOIUrl":"10.1007/s00262-026-04422-y","url":null,"abstract":"<p><p>Among adoptive immune cell therapies, cytokine-induced killer cell (CIK) therapy has demonstrated clear therapeutic relevance in multiple cancers, particularly clear cell renal cell carcinoma (ccRCC). Despite being clinically successful, the molecular signatures associated with the immune-regulatory role of these CIK cells in cancers remain elusive. Considering this, we systematically identified CIK expansion-induced genes (CIK-EIGs) from their transcriptome profiles and curated the CIK-EIG-anchored transcriptome framework across bulk and single-cell ccRCC datasets. Using comprehensive bioinformatics analysis, we next developed the CIK-EIG-anchored risk stratification (CIKRRS), which enabled reliable prediction of patient prognosis, correlated with the clinical-pathological course, and defined an immunologically inflamed but clinically unfavorable phenotype. Of interest, the integrative analyses highlighted TNFSF14 as one of the key functional modulators within the CIK-EIG-associated immune landscape, showing a strong association with cytotoxic immune signaling and cancer-immunity cycle activity. Subsequently, the functional assays verified that TNFSF14 significantly enhanced CIK-mediated tumor cell killing, degranulation, and cytokine production in ccRCC cell lines, confirming its role in enhancing CIK effector function. Taken together, our findings present a CIK-EIG-anchored transcriptomic and prognostic framework and highlight the potential relevance of TNFSF14 for further optimization of CIK-based immunotherapy in ccRCC patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978641","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":"β-hydroxybutyrate potentiates anti-tumor immunity by modulating cytotoxic CD8⁺ T cell responses.","authors":"Yupan Bai, Han Xue, Yujie Bao, Yue Pan, Jiayin Tang, Mengna Wang, Ying Wang, Jie Xu, Jing Huang","doi":"10.1007/s00262-026-04420-0","DOIUrl":"10.1007/s00262-026-04420-0","url":null,"abstract":"<p><p>Ketogenic diets (KDs) have been reported to influence tumor progression through metabolic and immunological modulation of the tumor microenvironment. β-hydroxybutyrate (βOHB), the predominant ketone body elevated by KD, functions not only as an energy substrate but also as a potent signaling metabolite. Despite its role in modulating the tumor microenvironment, the direct impact of βOHB on the function of CD8⁺ T cell, a key mediator of anti-tumor immunity, remains incompletely understood. Here, we demonstrate that βOHB suppresses tumor growth in multiple mouse tumor models by enhancing the accumulation, survival, and effector function of tumor-infiltrating CD8⁺ T cells. In contrast, acetoacetate does not exert comparable immunomodulatory effects. Mechanistically, βOHB upregulates the Tcf7-Lck signaling pathway by engaging with the cell surface receptor Hcar2, an effect potentially working in parallel with its role as an HDAC inhibitor. Knockdown of either Tcf7 or Hcar2 in CD8⁺ T cells abolishes the promoting effect of βOHB on CD8⁺ T function. Our findings elucidate a metabolite-immune axis that directly regulates the functional state of tumor-infiltrating CD8⁺ T cells and provide experimental evidence linking ketone metabolism to anti-tumor immune regulation.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984978","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":"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}