Inhibiting circATXN7 in T cells for KRAS-mutant cancers

Inhibiting cytotoxic T cell circATXN7, a histone lactylation-activated circular RNA that binds to and inactivates NF-κB, could help treat KRAS-mutant cancers, which produce high levels of lactic acid, by decreasing CD8⁺ T cell sensitivity to activation-induced cell death (AICD).

In peripheral CD8⁺ T cells isolated from healthy donors and exposed to lactic acid to promote AICD, four circular RNAs were identified as up-regulated in AICD-resistant T cells compared with baseline, and further experiments identified circATXN7 as a regulator of AICD resistance. ...