Therapeutic KRAS^G12C inhibition drives effective interferon-mediated antitumor immunity in immunogenic lung cancers.

ABSTRACT: Recently developed KRAS^G12C inhibitory drugs are beneficial to lung cancer patients harboring KRAS^G12C mutations, but drug resistance frequently develops. Because of the immunosuppressive nature of the signaling network controlled by oncogenic KRAS, these drugs can indirectly affect antitumor immunity, providing a rationale for their combination with immune checkpoint blockade. In this study, we have characterized how KRAS^G12C inhibition reverses immunosuppression driven by oncogenic KRAS in a number of preclinical lung cancer models with varying levels of immunogenicity. Mechanistically, KRAS^G12C inhibition up-regulates interferon signaling via Myc inhibition, leading to reduced tumor infiltration by immunosuppressive cells, enhanced infiltratio

SUBMITTER: Mugarza E 

PROVIDER: S-EPMC9299537 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature