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Tumor immunotherapy\u2014particularly immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapy\u2014has emerged as a transformative approach by activating and reprogramming anti-tumor immune responses. Despite these advances, significant challenges persist, including limited response rates to checkpoint inhibitors, the immunosuppressive nature of the tumor microenvironment (TME), and resistance mechanisms employed by tumor cells. Growing evidence suggests that immune cell senescence is a critical contributor to TME-driven immunosuppression. Senescent immune cells exhibit functional decline, elevated expression of inhibitory immune checkpoint molecules, and increased secretion of pro-inflammatory cytokines, collectively impairing anti-tumor immunity and reducing the efficacy of immunotherapy. This review highlights the role of immune cell senescence in shaping the immunosuppressive TME and driving resistance to immunotherapy. It further discusses emerging therapeutic strategies that combine immunotherapy with senescence-targeting interventions, aiming to provide novel insights into the development of more effective cancer treatment strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1656733","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:30:02Z","timestamp":1760679002000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance"],"prefix":"10.3389","volume":"16","author":[{"given":"Duolun","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyan","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/eus.0000000000000056","article-title":"Comments and illustrations of the European Federation of Societies for Ultrasound in Medicine contrast-enhanced ultrasound guidelines. 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