Interferon response and epigenetic modulation by <i>SMARCA4</i> mutations drive ovarian tumor immunogenicity.

ABSTRACT: Cell-intrinsic mechanisms of immunogenicity in ovarian cancer (OC) are not well understood. Damaging mutations in the SWI/SNF chromatin remodeling complex, such as SMARCA4 (BRG1), are associated with improved response to immune checkpoint blockade; however, the mechanism by which this occurs is unclear. We found that SMARCA4 loss in OC models resulted in increased cancer cell-intrinsic immunogenicity, characterized by up-regulation of long-terminal RNA repeats, increased expression of interferon-stimulated genes, and up-regulation of antigen presentation machinery. Notably, this response was dependent on STING, MAVS, and IRF3 signaling but was independent of the type I interferon receptor. Mouse ovarian and melanoma tumors with SMARCA4 loss demonstrated increased infil

SUBMITTER: Brodeur MN 

PROVIDER: S-EPMC11616711 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature