Mutation of SMARCA4 Induces Cancer Cell-Intrinsic Defects in the Enhancer Landscape and Resistance to Immunotherapy.

ABSTRACT: Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and other components of the innate immune

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12127800 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature