Cancer immunology, immunotherapy : CII最新文献

{"title":"Mast cells in tumors: dual roles and therapeutic potential.","authors":"Dekun Song, Guorong Yan, Guolong Zhang","doi":"10.1007/s00262-026-04477-x","DOIUrl":"https://doi.org/10.1007/s00262-026-04477-x","url":null,"abstract":"<p><p>Mast cells (MCs) are tissue-resident immune cells that accumulate in the tumor microenvironment (TME) and display marked functional plasticity. Rather than acting through fixed pro-tumor or anti-tumor phenotypes, tumor-associated MCs acquire functional programs shaped by tumor type, spatial localization, disease stage, and local microenvironmental cues. In this review, we organize these dual roles around cellular crosstalk, mediator release, angiogenic and lymphangiogenic regulation, and extracellular matrix remodeling. Through these interconnected mechanisms, MCs may either promote tumor progression by reinforcing immunosuppression, limiting effector T cell activity, and supporting vascular, lymphatic, and stromal remodeling, or contribute to tumor suppression by promoting tumor cell apoptosis, antigen presentation, cytotoxic immune-cell recruitment, and anti-tumor mediator release. We also examine MC responses to various cancer treatments, including physical treatment modalities, chemotherapy, immunotherapy, targeted therapy, and CAR-based cell therapies, and discuss how these responses may influence therapeutic efficacy and treatment-related toxicity. Furthermore, we highlight emerging MC-targeted strategies that either suppress their chronic pro-tumor secretion or intentionally induce acute anti-tumor degranulation. By deciphering the dual nature of MCs in cancer, this review underscores the potential for reprogramming MCs to improve tumor treatment outcomes.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical efficacy of iPSC-derived MUC1-targeted CAR-NK cells against esophageal squamous cell carcinoma.","authors":"Yuting Peng, Tian Guan, Yi Xiao, Shugeng Lin, Jijun Wu, Yan Lin, Juping Wang, Haoyu Zeng, Changchun Ma","doi":"10.1007/s00262-026-04493-x","DOIUrl":"10.1007/s00262-026-04493-x","url":null,"abstract":"<p><strong>Background: </strong>MUC1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but MUC1-targeted CAR-NK cells remain unexplored in this malignancy.</p><p><strong>Methods: </strong>MUC1 expression was assessed by IHC in 90 ESCC specimens, 47 paired adjacent normal tissues, and normal human organs. MUC1-targeted CAR-NK cells were generated from an iPSC platform. Antitumor activity was evaluated against patient-specific ESCC organoids (PSOs), primary ESCC cells, KYSE150 and KYSE140 cells using live/dead staining, CCK-8, and xCELLigence assays. In vivo efficacy was assessed in a KYSE140 xenograft model.</p><p><strong>Results: </strong>MUC1 was expressed in 70% (63/90) of ESCC cases versus 14.9% (7/47) of adjacent normal tissues (P < 0.001), with negligible expression in normal organs. Among MUC1-positive ESCCs, 88.9% and 42.8% showed > 50% and > 80% tumor cell positivity, respectively. iPSC-derived MUC1 CAR-NK cells exhibited > 95% CAR expression across iPSC, progenitor, and mature stages. Compared with controls, MUC1 CAR-NK cells elicited potent, antigen-specific cytotoxicity against MUC1-expressing ESCC PSOs, primary cells, KYSE150, and KYSE140 in vitro and significantly suppressed KYSE140 xenograft growth in vivo.</p><p><strong>Conclusion: </strong>iPSC-derived MUC1-targeted CAR-NK cells exert robust and specific antitumor efficacy against human ESCC, supporting clinical translation of this off-the-shelf cell therapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498177","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":"Adjuvant immunotherapy in high-risk stage II melanoma: real-world outcomes from a large multicenter retrospective study.","authors":"Vincenzo De Falco, Antonino Colloca, Giuseppe Argenziano, Marcella Scala, Michele Guida, Margaret Ottaviano, Maria Chiara Sergi, Mariacarmela Santarpia, Teresa Del Giudice, Antonio Maria Grimaldi, Silvana Cozzolino, Miriam Forte, Francesco Caraglia, Eleonora Cioli, Alfonso Esposito, Maria Cristina Giugliano, Francesca Sparano, Francesco Iovino, Salvatore Tolone, Giovanni Docimo, Giuseppe Colella, Mario Faenza, Renato Franco, Camila Scharf, Anna Russo, Luigi Formisano, Davide Ciardiello, Paolo Antonio Ascierto, Fortunato Ciardiello, Teresa Troiani","doi":"10.1007/s00262-026-04466-0","DOIUrl":"https://doi.org/10.1007/s00262-026-04466-0","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous melanoma (CM) is an aggressive cancer since early stages. Stage IIB/C CM present significant recurrence risk. Recently, adjuvant immunotherapy demonstrated to increase recurrence-free survival (RFS) in this setting.</p><p><strong>Objective: </strong>Assess safety and efficacy of adjuvant immunotherapy for stage IIB/C CM in a real-world setting.</p><p><strong>Methods: </strong>Stage IIB/C CM patients treated with adjuvant immunotherapy in eight centers from the \"Gruppo Oncologico Italia Meridionale\" (GOIM) were retrospectively investigated. Data were collected over a median follow-up of 16 months.</p><p><strong>Results: </strong>Ninety-six patients with a median age of 59 years were included. Most participants were male (64.6%). Approximately 60.4% were classified stage IIB and 39.6% stage IIC, with the majority of tumors localized on the trunk (54.2%). Toxicity occurred in 63.5% of patients with 79.7% of these events classified as grade 1-2 (CTCAE v5.0). The most reported events were thyroid dysfunction, fatigue, gastrointestinal disorders and itchiness. Recurrence was observed only in 7 patients (7.3%).</p><p><strong>Conclusions: </strong>The 12-month and 24-month RFS were respectively 98.7% and 82.6%. The toxicity profile was generally manageable in a real-life population, however 17.6% of all patients experienced grade 3-4 AEs, underscoring the importance of evaluating adjuvant therapy in a multidisciplinary setting.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBO1 suppresses anti-tumor immunity of CD8⁺ T Cells in thyroid cancer by recruiting BRD4 to regulate VTCN1 expression.","authors":"Yan Chen, Feng Zeng, Shan Liao, Yan Lei, Qian He, Yanhong Zhou, Yanling Li, Chen Long","doi":"10.1007/s00262-026-04491-z","DOIUrl":"10.1007/s00262-026-04491-z","url":null,"abstract":"<p><p>Thyroid cancer is the most common endocrine malignancy. Although surgery remains the primary treatment, advanced disease frequently recurs or metastasizes, and subsequent therapies yield suboptimal outcomes. Immunotherapy holds promise, yet the underlying immune-evasion mechanisms remain incompletely understood. HBO1, a multifunctional acyltransferase, plays a significant role in tumor immune regulation. Our previous research revealed that HBO1 is highly expressed in thyroid cancer tissues, promotes malignant progression, and inhibits CD8⁺ T cell function. To further elucidate the role and mechanism of HBO1 in thyroid cancer immune regulation, we conducted the following investigations. Firstly, using an in vitro co-culture model analyzed by flow cytometry and ELISA assays, we found that HBO1 overexpression induces CD8⁺ T cell apoptosis and significantly suppresses their cytotoxic function and secretion of effector molecules. Secondly, leveraging bioinformatic analysis of CUT&Tag datasets combined with in vitro cellular experiments, we found that HBO1 was associated with increased VTCN1 expression in an H3K14 acetylation-dependent manner, thereby contributing to CD8⁺ T cell dysfunction. Subsequently, employing RNA-seq analysis, ChIP-qPCR, dual-luciferase reporter assays, co-immunoprecipitation (Co-IP), and in vivo experiments, we further explored the underlying mechanism and found that HBO1 may facilitate BRD4 enrichment at the VTCN1 promoter through H3K14 acetylation, thereby promoting VTCN1 transcription and contributing to anti-tumor immune suppression in thyroid cancer. Finally, through IP-MS and Co-IP experiments, we identified the E3 ligase TRIM21 as a potential upstream regulator of HBO1. TRIM21 modulates HBO1 acetyltransferase activity by promoting its ubiquitination-mediated degradation, consequently influencing HBO1-associated immune escape in thyroid cancer. In summary, this study suggests that HBO1 may regulate VTCN1 expression through an H3K14ac-BRD4-associated mechanism in thyroid cancer, thereby contributing to suppression of CD8⁺ T cell anti-tumor immunity. In addition, TRIM21 may participate in the regulation of HBO1 protein stability and its associated immune-related signaling. Our findings provide new experimental evidence for understanding immune escape mechanisms and exploring potential immunotherapeutic targets in thyroid cancer.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475294","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":"Pilot report of an anti-PD-1/VEGF bispecific antibody for treating recurrent H3K27M-mutant diffuse midline gliomas.","authors":"Li Yanchu, Wang Hongbin, Yuan Xiaoli, Zhang Li, Wang Jun, Ren Meiling, Yang Xiaoyan, Liu Lei, Wang Feng","doi":"10.1007/s00262-026-04434-8","DOIUrl":"10.1007/s00262-026-04434-8","url":null,"abstract":"<p><strong>Background: </strong>H3K27M-mutant diffuse midline gliomas (DMGs) are highly aggressive, immunosuppressive tumors that are resistant to conventional therapies. Median overall survival is typically 8-11 months after diagnosis; fewer than 10% of patients survive beyond 2 years, and the 5-year survival rate is generally below 1%. Ivonescimab, a novel bispecific antibody that simultaneously targets PD-1 and VEGF, may help overcome this resistance by restoring T cell immunity and normalizing tumor vasculature. We report the first use of ivonescimab as salvage therapy for recurrent DMG.</p><p><strong>Methods: </strong>Two patients with recurrent H3K27M-mutant DMG who experienced rapid progression after standard first-line chemoradiotherapy received off-label ivonescimab (10 mg/kg) plus chemotherapy intravenously every 3 weeks for 5-6 cycles.</p><p><strong>Results: </strong>After only three cycles, MRI revealed marked tumor shrinkage and substantial improvement in Karnofsky Performance Status (KPS). At treatment completion, both patients achieved partial remission (PR, tumor volume decreased at 66.7% and 68.7%, respectively). Both patients maintained progression-free survival (PFS) of more than 8 months and overall survival (OS) of more than 16 months, and both were alive more than 10 months after recurrence. Furthermore, treatment was well tolerated, the most common adverse event was fatigue, hematology toxicity and nausea vomiting, and no grade 3 or higher adverse events were observed.</p><p><strong>Conclusions: </strong>These preliminary findings demonstrate the tolerability of concurrent anti-PD-1/VEGF bispecific antibody with chemotherapy for recurrent DMG, who do not fit for reRT, and suggests that combination therapy may offer survival benefit. However, larger and more rigorous studies are needed to validate these initial observations and to define the efficacy and safety of this strategy in the clinical management of DMG.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440710","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":"Survival outcomes of conversion curative therapy following atezolizumab-bevacizumab in advanced hepatocellular carcinoma.","authors":"Ying-Hsin Chen, Wei-Feng Li, Yen-Hao Chen, Ming-Chao Tsai, Yuan-Hung Kuo, Jing-Houng Wang, Chien-Hung Chen, Sheng-Nan Lu, Chih-Chi Wang, Chao-Hung Hung","doi":"10.1007/s00262-026-04476-y","DOIUrl":"10.1007/s00262-026-04476-y","url":null,"abstract":"<p><strong>Background: </strong>The prognostic value of curative therapies-including liver transplantation, hepatectomy, and local ablation-in patients with advanced hepatocellular carcinoma (HCC) following atezolizumab plus bevacizumab treatment remains unclear. This study evaluated the feasibility of curative therapy and compared survival outcomes between patients who did and did not undergo curative interventions following atezolizumab plus bevacizumab, using a propensity score-matched (PSM) analysis.</p><p><strong>Methods: </strong>We retrospectively analyzed 318 consecutive patients with advanced HCC who received atezolizumab plus bevacizumab between 2020 and 2024. Overall survival (OS) and progression-free survival (PFS) were defined as the primary and secondary endpoints, respectively. Survival outcomes were estimated using the Kaplan-Meier method and evaluated with multivariate Cox proportional hazards regression, modeling exposure to conversion curative therapy as a time-dependent covariate.</p><p><strong>Results: </strong>The objective response rate to atezolizumab plus bevacizumab was 34.6%. Thirty-six patients (11%) subsequently underwent curative therapy, including liver transplantation (n = 8, 2.5%), hepatectomy (n = 11, 3.5%), and local ablation (n = 17, 5.3%). Patients receiving curative therapy demonstrated significantly improved OS (p < 0.001) and PFS (p < 0.001) compared with those who did not, with benefits persisting after PSM analysis. Multivariate Cox regression identified curative therapy as an independent predictor of OS (hazard ratio [HR] 0.398; 95% confidence interval [CI] 0.179-0.885; p = 0.024).</p><p><strong>Conclusions: </strong>In selected patients with advanced HCC who achieved disease control after atezolizumab-bevacizumab, conversion curative therapy was associated with favorable survival outcomes.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431881","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":"Effectiveness and safety of enfortumab vedotin and pembrolizumab in a real-world patient population with urothelial carcinoma: results from a multi-institutional cohort (GUARDIANS).","authors":"Stefanie Zschäbitz, Irfan Bhatti, Jozefina Casuscelli, Ludwig Otto Pachmayr, Thomas Büttner, Thomas Elegeert, Nina Holzwarth, Severin Rodler, Martin Hennig, Emily Rinderknecht, Muammar Dib, Katrin Schlack, Christopher Darr, Anna-Lisa Volk, Philipp Schmucker, Friedemann Zengerling, Pia Paffenholz, Joschka Heil, Eva Erne, Subhajit Mandal, Frederik Wessels, Thea Maria Busse, Daniel Seidl, Susan Foller, Alexander Höllein, Tim Nestler, Christian Gratzke, Louis Rhode, Jakob Kohler, Günter Niegisch, Anna Katharina Seitz, Julia Heinzelbecker, Niklas Klümper, Margitta Retz, Viktor Grünwald, Can Aydogdu, Marco Julius Schnabel","doi":"10.1007/s00262-026-04448-2","DOIUrl":"10.1007/s00262-026-04448-2","url":null,"abstract":"<p><strong>Introduction: </strong>Enfortumab vedotin plus pembrolizumab (EVP) is the standard first-line treatment for metastatic or locally advanced urothelial carcinoma (m/laUC). Real-world patients frequently present with unfavorable clinical characteristics, raising uncertainty about whether outcomes mirror those of the pivotal EV-302/KEYNOTE-A39 trial. This study assessed effectiveness and safety of EVP in a real-world cohort of patients with m/laUC.</p><p><strong>Materials and methods: </strong>Retrospective multicenter study including patients treated with EVP across 25 German hospitals (between 03/2022 and 08/2025). Treatment delivery and monitoring followed local clinical standards. Adverse events (AEs) were documented per CTCAE v5.0. Responses were assessed locally using RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methodology.</p><p><strong>Results: </strong>A total of 468 patients (median age = 69 years) were included. The overall response rate (ORR) was 50.2% (partial response:37.4%, complete response:12.8%). Median PFS was 10.2 months (95%CI,8.0-12.7). 12-month and 24-month OS rates were 71.9% and 60.6%, respectively. ECOG PS 0-1 and occurrence of skin toxicity were associated with improved outcomes. Any-grade AEs occurred in 81.8% and grade ≥ 3 AEs in 35.8%. Peripheral sensory neuropathy and skin toxicity were the most common AEs. Ten treatment-related fatal events were recorded.</p><p><strong>Conclusions: </strong>EVP demonstrated robust effectiveness and manageable toxicity in a large and diverse real-world cohort including patients with divergent histology. Skin toxicity was associated with superior ORR, PFS, and OS. Our findings support EVP as an effective first-line option for patients with m/laUC treated outside clinical trials.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431908","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: APC-targeted DNA vaccines: the role of CCL19 in immune cell recruitment and early onset of the immune response.","authors":"Marina Barrio-Calvo, Stine Friis, Søren Vester Kofoed, Sofie Cens Holste, Rasmus Ohrt Andersen, Birgitte Rønø, Gertrud Malene Hjortø","doi":"10.1007/s00262-026-04412-0","DOIUrl":"10.1007/s00262-026-04412-0","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428471","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":"Efficacy of checkpoint inhibitors in genitourinary cancers with advanced chronic kidney disease.","authors":"Yin-Shen Chen, Chia-Cheng Yu, Renin Chang, Sheng-Hua Wu, Cheuk-Kwan Sun, Shu-Hung Huang","doi":"10.1007/s00262-026-04482-0","DOIUrl":"10.1007/s00262-026-04482-0","url":null,"abstract":"<p><strong>Background: </strong>Immunological checkpoint inhibitors (ICIs) have shown promise in treating various malignancies but are understudied in genitourinary cancers among patients with advanced chronic kidney disease (CKD), who are typically excluded from clinical trials. We evaluated the efficacy and safety of ICIs in this high-risk patient group.</p><p><strong>Methods: </strong>This retrospective cohort study included patients with CKD diagnosed with renal cell carcinoma and urothelial carcinoma, utilizing data from 63 healthcare organizations in the TriNetX US Collaborative Network database between January 2015 and December 2023. Patients with advanced CKD (aCKD) and early CKD (eCKD) receiving ICIs were compared after 1:1 propensity score matching. Outcomes were assessed using Kaplan-Meier and Cox proportional hazards models. The primary outcome was all-cause mortality, and secondary outcomes included immune-related adverse events (irAEs).</p><p><strong>Results: </strong>The study involved 2213 patients with aCKD and 9784 with eCKD who received ICIs. After matching, 2196 patients remained in each cohort. Patients with aCKD had higher 2-year all-cause mortality than those with eCKD (44.7% vs. 35.5%; HR = 1.372, 95% CI: 1.248-1.507). They also had a modestly higher risk of overall coded irAEs (HR = 1.141, 95% CI: 1.058-1.231), mainly driven by AKI (HR = 1.662, 95% CI: 1.500-1.840). Increased risks of mortality and AKI were evident from 3 months and persisted through 60 months.</p><p><strong>Conclusions: </strong>In this large retrospective database study, aCKD was associated with worse survival and greater renal vulnerability among ICI-treated patients with genitourinary cancers. CKD alone should not automatically preclude ICI use in carefully selected patients, but close renal monitoring and multidisciplinary management are warranted, particularly for patients with aCKD.</p><p><strong>Trial registration number: </strong>Not applicable.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428453","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":"Association between cumulative lifetime exposure to reproductive hormones and tumor-infiltrating lymphocytes, CD4 +, and CD8 + T cells among women with breast cancer.","authors":"Yidan Zhang, Rand T Akasheh, Angela R Omilian, Bo Qin, Nur Zeinomar, Song Yao, Chi-Chen Hong, Elisa V Bandera, Christine B Ambrosone, Thaer Khoury, Ting-Yuan David Cheng","doi":"10.1007/s00262-026-04471-3","DOIUrl":"10.1007/s00262-026-04471-3","url":null,"abstract":"<p><strong>Background: </strong>Reproductive hormones may influence immune responses to tumors. Tumor-infiltrating lymphocytes (TILs), CD4 +, and CD8 + T cell densities are markers of immune activity and breast cancer prognosis. We examined associations between lifetime reproductive hormone exposure, tumor immune infiltration, and survival among women with breast cancer.</p><p><strong>Methods: </strong>The study included invasive breast cancer cases in the Women's Circle of Health Study and the Women's Circle of Health Follow-up Study. Lifetime endogenous hormone exposure (LHEendo) was defined as reproductive years plus pregnancy duration minus breastfeeding duration; lifetime exogenous hormone exposure (LHEexo) was defined as the combined cumulative duration of oral contraceptive and hormone replacement therapy use. TILs were scored as ordered percentage values from 0 to 100% stromal area; CD4 + /CD8 + T cell densities were quantified by immunohistochemistry. TILs were modeled using ordinal logistic regression, and CD4 + /CD8 + T cell densities were modeled using gamma generalized linear models among participants with positive density values, with covariates selected by directed acyclic graphs. Overall survival was assessed using Cox proportional hazards models, and breast cancer-specific survival was assessed using Fine-Gray competing-risk models.</p><p><strong>Results: </strong>Among 1195 women with valid TILs measurements, 553 and 610 had CD4 + and CD8 + T cell density data, respectively. Across all tumor molecular subtypes, a 1-year increment of LHEendo was associated with a 2.85% decrease in CD8 + T cell density (95% CI - 5.14%, - 0.61%). LHEendo was associated with lower odds of being in a higher TIL level among women with hormone receptor (HR) + /HER2- tumors (OR = 0.977, 95% CI 0.957, 0.997), although the interaction by molecular subtype was not statistically significant. LHEexo was associated with lower risk of all-cause mortality (HR = 0.979, 95% CI 0.960, 0.998). TIL-stratified analyses suggested that this association may be more apparent among women with TILs ≥ 50% (HR = 0.90, 95% CI = 0.82, 0.99; P-interaction = 0.10).</p><p><strong>Conclusions: </strong>Lifetime endogenous hormone exposure was associated with lower CD8 + T cell density overall, with exploratory findings of lower TIL levels among women with HR + /HER2- tumors. Lifetime exogenous hormone exposure was associated with a lower risk of all-cause mortality, with possible variation by TIL levels.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428414","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}