By applying subcutaneous and orthotopic cancer murine models and an in vitro cell culture system mimicking the TME, we have demonstrated that H3K79me2‐FOXM1 plays a crucial role in accelerating pancreatic cancer and colon cancer progression by attenuating antitumor responses including BMDC maturation, cytokine secretion, and T‐cell activation. Here, FOXM1 is linked to pancreatic neoplasm.