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Elevated lactate levels, a hallmark of the Warburg effect, contribute to immune suppression through CD8+ T cell functionality and by promoting regulatory T cell (Treg) activity. Lactylation, a post-translational modification (PTM), alters histone and non-histone proteins, influencing gene expression and further reinforcing immune suppression. In the complex TME, lactate and its derivative, lactylation, are not only associated with immune suppression but can also, under certain conditions, exert immunostimulatory effects that enhance cytotoxic responses. This review describes the dual roles of lactate and lactylation in T-cell-mediated tumor immunity, analyzing how these factors contribute to immune evasion, therapeutic resistance, and immune activation. Furthermore, the article highlights emerging therapeutic strategies aimed at inhibiting lactate production or disrupting lactylation pathways to achieve a balanced regulation of these dual effects. These strategies offer new insights into overcoming tumor-induced immune suppression and hold the potential to improve the efficacy of cancer immunotherapies.<\/jats:p>","DOI":"10.3390\/biom14121646","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"1646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhi-Nan","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China"},{"name":"Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Tan","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China"},{"name":"The Third Clinical Medical College of Yangtze University, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China"},{"name":"Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China"},{"name":"Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China"},{"name":"School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7675-1845","authenticated-orcid":false,"given":"Zhaowu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China"},{"name":"School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1038\/s41467-021-25282-3","article-title":"Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity","volume":"12","author":"Weigelin","year":"2021","journal-title":"Nat. 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