{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:45:25Z","timestamp":1785375925490,"version":"3.55.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>The past decade has witnessed a paradigm shift in the treatment of bladder cancer, propelled by significant advances in immunotherapy. Immune checkpoint inhibitors (ICIs) targeting PD-1\/PD-L1 and CTLA-4, adoptive cellular therapies including chimeric antigen receptor T-cell (CAR-T) therapy, oncolytic viruses, and novel immunomodulatory agents have transformed the therapeutic landscape for both non\u2013muscle-invasive bladder cancer (NMIBC) and advanced urothelial carcinoma (UC). This review provides a comprehensive analysis of recent advances in bladder cancer immunotherapy, with a focus on underlying molecular and cellular mechanisms, key clinical trial evidence, and emerging resistance pathways. We highlight the rapidly expanding therapeutic roles of ICIs, alongside innovative modalities such as CAR-T cell therapy directed against tumor-associated antigens\u2014including NECTIN4, PSMA, and FR\u03b1. Emerging immunotherapeutic targets and therapeutic modalities are comprehensively reviewed. We critically evaluate key clinical trials and systematically assess combination strategies\u2014including ICIs combined with chemotherapy, radiotherapy, targeted therapy, or antibody\u2013drug conjugates (ADCs). Key determinants of the tumor microenvironment (TME)\u2014such as immunosuppressive cell populations, regulatory cytokines, and metabolic barriers\u2014are examined in the context of their roles in mediating therapeutic resistance. Biomarkers predictive of treatment response\u2014including PD-L1 expression and tumor mutational burden\u2014are summarized, integrating recent clinical and translational evidence. We conclude by outlining future research directions focused on overcoming therapeutic resistance, refining predictive and prognostic biomarkers, and developing next-generation immunotherapies to improve clinical outcomes for patients.<\/jats:p>","DOI":"10.3389\/fonc.2026.1786965","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:23:16Z","timestamp":1773638596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Recent advances in immunotherapy for bladder cancer: mechanisms, clinical applications, and future perspectives"],"prefix":"10.3389","volume":"16","author":[{"given":"Rui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, 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