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As T cells age, especially within the tumor microenvironment, they undergo significant metabolic shifts that may hinder their proliferation and functionality. This manuscript reviews how metabolic alterations contribute to T cell senescence in cancer and discusses potential therapeutic strategies aimed at reversing these metabolic changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, and lipid metabolism adjustments that could rejuvenate senescent T cells, potentially restoring their efficacy in tumor suppression. This review also focuses on the significance of metabolic interventions in T cells with aging and further explores the future direction of the metabolism-based cancer immunotherapy in senescent T cells.<\/jats:p>","DOI":"10.1038\/s41420-025-02468-y","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T17:08:01Z","timestamp":1744218481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy"],"prefix":"10.1038","volume":"11","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanying","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3358-9873","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9662-8904","authenticated-orcid":false,"given":"Siyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2706-2123","authenticated-orcid":false,"given":"Linze","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"2468_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101834","volume":"70","author":"KM Quinn","year":"2023","unstructured":"Quinn KM, Vicencio DM, La Gruta NL. 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