Another major recent advance has been the discovery that HIFs play critical roles in mediating the ability of cancer cells of many types, including breast, colorectal, and liver cancer, to evade killing by the immune system and that small-molecule inhibitors of HIF-1 and HIF-2 dramatically improve the response to immune checkpoint inhibitors (anti-CTLA4, anti–PD-1 or anti–PD-L1 antibody) in mouse models (13, 14). This evidence concerns the gene HIF1A and cancer.