EPAS1 and neoplasm: In TME, lactic acid alters the TAM phenotype to acquire tumor growth-enhancing properties, lactate inhibits TFEB-mediated expression of the macrophage-specific vesicular ATPase subunit, ATP6V0d2, by activating mTORC1, resulting in HIF-2α lysosomal degradation and programming of TAMs to a tumor growth-promoting immunophenotype [111].