Authors
Da Kang, Song-Zuo Xie, Yong-Zhou Luo, Xin-Pei Deng, Xi-Rong Tan, Ze-Geng Chen, Ling-Xing Zeng, Gong Chen, Pei-Rong Ding, Zhi-Zhong Pan, Rong-Xin Zhang
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e76143. Jun 15, 2026. Epub Jun 15, 2026.
Abstract
ADAR1-mediated RNA editing has been implicated in tumor immune evasion, primarily through tumor-intrinsic interferon (IFN) signaling. However, its cell-type-specific roles within immune compartments, particularly T cells, remain unclear in colorectal cancer (CRC). RNA editing landscapes were profiled using bulk RNA sequencing and full-length single-cell RNA sequencing. ADAR1 expression and RNA editing activity were analyzed across the tumor microenvironment (TME), followed by functional validation and multi-cohort clinical evaluation. Single-cell analyses revealed elevated ADAR1 activity in tumor-infiltrating T cells, defining an exhausted and proliferative T cell state associated with immune dysfunction. Functional experiments demonstrated that ADAR1 promotes T-cell 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-β-SMAD signaling pathway. Clinically, elevated ADAR1 expression in T cells was associated with reduced response to anti-PD-1 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.
PMID:
42295773
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 11
- Comments 0