Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma.

ABSTRACT: Increasing evidence indicates that activation of oncogenic pathways contributes to an unfavourable tumour immune microenvironment (TIME), ultimately resulting in resistance to immunotherapy. Here, we aim to identify a critical oncogenic pathway involved in an antigen-expressing c-MYC-lucOS^OE/Tp53^KO hepatocellular carcinoma (HCC) mouse model that simulates immune response against tumour-associated antigens. Using data-independent acquisition proteomics, we reveal the role of wild-type KRAS in immune escaped mouse HCC tumours, with EGF concurrently activating EGFR/MEK/ERK signalling. Single cell RNA sequencing data analysis reveals that KRAS signalling intrinsically inhibits interferon-mediated MHC-I expression and extrinsically impairs CD8⁺ T cell activity d

SUBMITTER: Lei MML 

PROVIDER: S-EPMC12606110 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature