For some cancers, including breast, pancreatic, colorectal, and prostate cancers, a high proportion of non-responders has been reported, one of the main causes of which is hypoxic stress.208 Hypoxia-induced HIF-1α can promote programmed death ligand-1 (PD-L1) expression in cancer cells and suppress immune effects.209 Moreover, hypoxia plays a central role in cancer progression and resistance to therapy by promoting various changes in the biology of stromal cells in the TME, including immune cells. The gene discussed is HIF1A; the disease is cancer.