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Here, we demonstrated that tumor\u2010intrinsic ARHGEF3 reprogrammed the tumor microenvironment into a T\u2010cell\u2010inflamed state, resulting in potent antitumor effects. Mechanistically, ARHGEF3 functioned as a guanine nucleotide exchange factor that activated the RHOA\u2010ROCK\u2010PTEN cascade and inhibited AKT signaling. This inhibition upregulated IRF1\u2010dependent chemokines CXCL10 and CXCL11 to drive T\u2010cell infiltration, while suppressing FASN\u2010mediated fatty acid synthesis to limit myeloid cell\u2010mediated immunosuppression. The dual effects elicited robust T\u2010cell immunity and overcame tumor resistance to immunotherapy. In human tumors,\n                    <jats:italic>ARHGEF3<\/jats:italic>\n                    expression correlated positively with T\u2010cell\u2010inflamed signatures, improved clinical outcomes, and responsiveness to immunotherapy. Collectively, these findings identify ARHGEF3 as a key modulator linking chemokine signaling with lipid availability to shape T\u2010cell immunity, offering a promising therapeutic strategy to overcome immunotherapy resistance.\n                  <\/jats:p>","DOI":"10.1002\/advs.202523895","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:41:44Z","timestamp":1776951704000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor\u2010Intrinsic ARHGEF3 Enhances Antitumor Immunity by Promoting T\u2010Cell Infiltration and Limiting Myeloid Cell\u2010Mediated Immunosuppression"],"prefix":"10.1002","volume":"13","author":[{"given":"Yue","family":"Li","sequence":"first","affiliation":[{"name":"Science and Technology Innovation Center Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"The Third 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