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Here, we show that induced Treg depletion in mice selectively unleashes IFN\u03b3-producing \u03b3\u03b4 T cells, which are required for tumor control in an orthotopic breast cancer model. Treg cells outcompete IFN\u03b3+ \u03b3\u03b4 T cells for IL-2 due to increased expression of the high-affinity IL-2 receptor, thereby limiting the proliferation and effector functions of IFN\u03b3+ \u03b3\u03b4 T cells. Consistently, in vivo neutralization of IL-2 alongside Treg depletion abrogates the induction of IFN\u03b3+ \u03b3\u03b4 T cell responses, whereas administration of an IL-2R\u03b2\u03b3c agonist circumvents Treg-mediated suppression and enhances tumor control. Finally, Treg cells also inhibit endogenous and expanded human \u03b3\u03b4 T-cells, which can be rescued by IL-2R\u03b2\u03b3c agonism to enhance therapeutic responses in xenografted mice. Thus, bypassing Treg-mediated suppression may improve the outcome of \u03b3\u03b4 T cell\u2013based immunotherapies.<\/jats:p>","DOI":"10.1084\/jem.20252133","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:23:12Z","timestamp":1776838992000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Regulatory T cells sabotage anti-tumor \u03b3\u03b4 T cells by creating IL-2\u2013deficient environments"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-8699","authenticated-orcid":true,"given":"Rafael","family":"Blanco-Dom\u00ednguez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0346k0491","id-type":"ROR","asserted-by":"publisher"}],"name":"Gulbenkian Institute for Molecular Medicine 1 , 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