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However, its cell\u2010type\u2010specific roles within immune compartments, particularly T cells, remain unclear in colorectal cancer (CRC). RNA editing landscapes were profiled using bulk RNA sequencing and full\u2010length single\u2010cell RNA sequencing. ADAR1 expression and RNA editing activity were analyzed across the tumor microenvironment (TME), followed by functional validation and multi\u2010cohort clinical evaluation. Single\u2010cell analyses revealed elevated ADAR1 activity in tumor\u2010infiltrating T cells, defining an exhausted and proliferative T cell state associated with immune dysfunction. Functional experiments demonstrated that ADAR1 promotes T\u2010cell exhaustion and impairs cytotoxic activity. In vivo adoptive transfer models further confirmed that ADAR1 overexpression in T cells limits antitumor efficacy. Mechanistically, ADAR1 activated the TGF\u2010\u03b2\u2010SMAD signaling pathway. Clinically, elevated ADAR1 expression in T cells was associated with reduced response to anti\u2010PD\u20101 therapy across immunotherapy cohorts. These findings identify ADAR1 as a key regulator of dysfunctional T cell states in CRC and suggest that targeting ADAR1 activity in T cells may represent a promising strategy for improving immunotherapy efficacy and developing predictive biomarkers.<\/jats:p>","DOI":"10.1002\/advs.76143","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:26:49Z","timestamp":1781537209000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell RNA Editing Identifies T Cell ADAR1 as a Key Regulator of Immune Exhaustion and Anti\u2010PD\u20101 Resistance in Colorectal Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Da","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Sun Yat\u2010sen University Cancer Center  Guangzhou Guangdong Province P. R. 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