Furthermore, this treatment drastically lowered tumor weight and reduced iTreg abundance while increasing the percentage of CD8+ T cells in the meantime [183, 337]. Hypoxia-inducible factors (HIFs), first discovered by Semenza and Wang in 1992, are the predominant regulators of the response to hypoxia, and HIF-2α was found to be indispensable for Treg functions. Here, EPAS1 is linked to neoplasm.