In light of the accumulating evidence that HIFα are directly and indirectly involved in many of the innate and adaptive immune pathways including the expression of immune checkpoints, a combination of drugs able to inhibit HIFα, particularly HIF-1α, with antibodies against immune checkpoints may represent a novel and more reliable approach to cancer immunotherapy, especially for patients whose tumors are treated with SABR. This evidence concerns the gene HIF1A and cancer.