Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer.

ABSTRACT: AT-rich interactive domain-containing protein 1A (ARID1A), a core constituent of the switch/sucrose nonfermentable (SWI/SNF) complex, is mutated in approximately 10% of colorectal cancers. Whereas ARID1A deficiency corresponds to heightened immune activity in colorectal cancer, immune checkpoint inhibitors (ICI) have shown limited efficacy in these tumors. The discovery of targetable vulnerabilities associated with ARID1A deficiency in colorectal cancer could expand treatment options for patients. In this study, we demonstrated that arachidonic acid (AA) metabolism inhibitors synergize with ICIs in ARID1A-deficient colorectal cancer by enhancing the activity of CD8+ T cells and inhibiting vasculogenic mimicry. Epigenetic analysis using ATAC-seq and ChIP-qPCR revealed that the lack of ARID1

SUBMITTER: Cui L 

PROVIDER: S-EPMC11873721 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature