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Increasing evidence indicates that the immunosuppressive tumor immune microenvironment (TIME) is a major obstacle to effective antitumor immunity, with regulatory T cells (Tregs) emerging as the central cellular mediators of this process. Tumor-infiltrating Tregs possess potent immunosuppressive functions and suppress cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated responses through multiple mechanisms, including interleukin-2 consumption, cytotoxic T-lymphocyte-associated protein 4-dependent inhibitory signaling, and secretion of immunosuppressive cytokines. Recent advances in spatial transcriptomics and single-cell technologies have catalogued substantial functional heterogeneity among Tregs and revealed their preferential accumulation at tumor margins, suggesting a potential link to immune-excluded TIME phenotypes. In this review, we summarize the known Treg-mediated immunosuppressive mechanisms in gastrointestinal cancers, highlight their spatial and functional characteristics within the TIME, and discuss the status of current Treg-targeted immunotherapeutic strategies and possible future strategies to overcome ICI resistance.\n                  <\/jats:p>","DOI":"10.1007\/s10147-026-02990-8","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:14:00Z","timestamp":1778526840000},"page":"2589-2597","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting regulatory T cells in gastrointestinal cancers: current status and future perspectives"],"prefix":"10.1007","volume":"31","author":[{"given":"Koichi","family":"Jinushi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1733-5064","authenticated-orcid":false,"given":"Takuro","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Doki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"2990_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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