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However, the precise mechanisms by which STING regulates gamma\u00a0delta\u00a0(\u03b3\u03b4) T cell function during tumor progression remain unclear. Herein, we find that tumor\u2010derived cyclic GMP\u2010AMP (cGAMP) activates a distinct STING pathway by inducing TBK1\u2010mediated phosphorylation of Eomes in \u03b3\u03b4 T cells during the early stage of tumor development is demonstrated. This activation leads to interferon\u2010gamma (IFN\u2010\u03b3) production and consequent tumor surveillance. However, at advanced stages of tumor progression, the accumulation of immune\u2010suppressive cytokine transforming growth factor\u2010beta (TGF\u2010\u03b2) downregulates STING levels, compromising the function of \u03b3\u03b4 T cells. Notably, the synergism between TGF\u2010\u03b2 inhibition and STING agonists effectively counteracts the immunosuppressive tumor microenvironment, thereby augmenting the antitumoral effects of \u03b3\u03b4 T cells. These findings present a novel mechanism involving STING\u2010mediated IFN\u2010\u03b3 production in \u03b3\u03b4 T cells and hold significant implications for the development of potent immunotherapeutic approaches against cancer.<\/jats:p>","DOI":"10.1002\/advs.202404432","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T02:54:54Z","timestamp":1732244094000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["\u03b3\u03b4 T Cell\u2010mediated Tumor Immunity is Tightly Regulated by STING and TGF\u2010\u03b2 Signaling Pathways"],"prefix":"10.1002","volume":"12","author":[{"given":"Jing","family":"Luo","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Institute of Translational Medicine Zhuhai People's Hospital Affiliated with Jinan University Jinan University  Zhuhai 519000 P. R. 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