EPAS1 and cancer: VEGF-A levels in cancers are inversely correlated with CD8+ T cell levels.221 Loss of HIF-1α decreases the ratio of CD8+ to FOXP3+ cells in TILs.229 After antigenic restimulation, the generation of effector cytokines from HIF-1α mutant T cells was suppressed.221 Ectopic HIF-2α (but not HIF-1α) mediates the extensive changes in gene expression by altering the CD8+ T cell transcription factor network, regardless of VHL inhibition, including increased perforin, granzyme B, IL-2, integrins, and CXCR4.