Targeting the vulnerability of arachidonic acid metabolism to enhance immunotherapy efficacy in ARID1A-deficient colorectal cancer [RNA-Seq]

ARID1A, a core constituent of SWI/SNF complex, is mutated in about 10% of colorectal cancer (CRC). This study demonstrates a synergistic effect of arachidonic acid metabolism inhibitors with immune checkpoint inhibitors (ICIs) by regulating functionality of CD8+ T cells and vasculogenic mimicry (VM) formation in ARID1A-deficient CRC. Mechanistically, ATAC-seq and ChIP-qPCR demonstrated that the lack of ARID1A results in reduced levels of the key enzymes PTGS1 and PTGS2, which control the arachidonic acid pathway. This reduction generated a reliance on the remaining functionality of arachidonic acid pathway in ARID1A-deficient cells.