Interestingly, pyruvate kinase M2 (PKM2) and HIF-1α can bind directly to hypoxia response element (HRE) sites on the PD-L1 (programmed death-ligand 1) promoter to upregulate PD-L1 expression by macrophages and promote tumor growth by restraining CD8+ T cell responses [67]. The gene discussed is CD8A; the disease is neoplasm.