DNMT inhibition epigenetically restores the cGAS-STING pathway and activates RIG-I/MDA5-MAVS to enhance antitumor immunity.

ABSTRACT: The cGAS-STING cytosolic DNA-sensing pathway is a key mediator of the innate immune response and plays a crucial role in antitumor immunity. The expression of cGAS and STING is often suppressed in tumor cells, and reduced expression is associated with poor prognosis and inferior response to immunotherapy. In this study we systematically investigated the expression pattern of cGAS-STING pathway in tumors and its correlation with immunotherapy response. We showed that the expression of cGAS and STING was significantly decreased or undetectable in most breast cancer and murine tumor cell lines, while high cGAS and STING expression was associated with increased T cell infiltration, elevated PD-L1 and PD-1 levels, improved immunotherapy response and prolonged survival. In cGAS-STING-deficient M

SUBMITTER: Tu Y 

PROVIDER: S-EPMC12764874 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature