EPAS1 and cancer: In contrast to the large body of data presented above indicating that HIF activity in cancer cells drives immune evasion, studies focused on the conditional KO of HIFs in immune cell populations have reported that HIFs play important cell-autonomous roles in CD4+ and CD8+ effector T cells, MDSCs, TAMs, Th17 cells, and NK cells; however, many of these studies have revealed distinct roles for HIF-1α versus HIF-2α, and distinct effects of loss of function in the same immune cell type in different tumor models (39).