Elimination of oncogenic KRAS in genetic mouse models eradicates pancreatic cancer by inducing FAS-dependent apoptosis by CD8⁺ T cells.

ABSTRACT: Oncogenic KRAS^G12D (KRAS^∗) is critical for the initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC) and is a known repressor of tumor immunity. Conditional elimination of KRAS^∗ in genetic mouse models of PDAC leads to the reactivation of FAS, CD8⁺ T cell-mediated apoptosis, and complete eradication of tumors. KRAS^∗ elimination recruits activated CD4⁺ and CD8⁺ T cells and promotes the activation of antigen-presenting cells. Mechanistically, KRAS^∗-mediated immune evasion involves the epigenetic regulation of Fas death receptor in cancer cells, via methylation of its promoter region. Furthermore, analysis of human RNA sequencing identifies that high KRAS expression in PDAC tumors shows a l

SUBMITTER: Mahadevan KK 

PROVIDER: S-EPMC10810082 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature