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However, the precise role of CYP4X1 and sEH in tumor immune evasion is poorly understood. Here, it is elucidated that CYP4X1\/sEH\u2010dependent endocannabinoid metabolism governs immune evasion in colon cancer by promoting the infiltration of regulatory T cells (Tregs) and impairing CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell effector function. Mechanistically, CYP4X1\/sEH\u2010derived 14,15\u2010EET\u2010EA upregulates PD\u2010L1, CXCL12, and TGF\u2010\u03b2 in cancer\u2010associated fibroblasts (CAFs) via the GPR119\u2010Gs\/\u03b2\u2010arrestin 2 signaling axis. Importantly, targeted regulation of the CYP4X1\/sEH\u2010GPR119 axis enhances the efficacy of anti\u2010PD\u20101 therapy. Moreover, CYP4X1 and sEH levels jointly predict prognosis and immune infiltration in human colon cancer. Together, this study highlights that CYP4X1\/sEH\u2010dependent endocannabinoid metabolism controls CAF\u2010mediated immune evasion, and targeting the CYP4X1\/sEH\u201014,15\u2010EET\u2010EA\u2010GPR119 axis represents a promising therapeutic strategy for improving anti\u2010PD\u20101 therapy in colon cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.202507695","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T05:30:20Z","timestamp":1763962220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CYP4X1\/sEH\u2010Dependent Endocannabinoid Metabolism Drives Fibroblast\u2010Mediated Immunosuppression to Limit Immunotherapy in Colon Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5047-5573","authenticated-orcid":false,"given":"Min","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Hubei 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