<p>Nature Communications, Published online: 27 February 2026; <a href="https://www.nature.com/articles/s41467-026-69796-0">doi:10.1038/s41467-026-69796-0</a></p>Efficacy of chimeric antigen receptor (CAR)-T in solid tumors are limited by the antigen heterogeneity and tumor microenvironment (TME) induced exhaustion. The authors here manifested that Nr2f6-deficient CAR-T cells have superior anti-tumor effect compared with traditional CAR-T cells, which is associated with enhanced cytotoxic function, followed by durable response due to epitope spreading.