The ANGPTL2–α5β1‐integrin pathway in tumor cells accelerates polycomb repressive complex 2‐mediated repressive histone modification at the major histocompatibility complex class I (MHC‐I) promoter via JARID2 induction, thereby attenuating interferon γ‐induced MHC‐I expression in tumor cells. Here, ANGPTL2 is linked to neoplasm.