IRF1 and hereditary clear cell renal cell carcinoma: Interestingly, other studies in renal cell carcinoma and melanoma observed the opposite effect, in which increasing TET-dependent demethylation substrates, like vitamin C and α-KG, improved TET2 activity at the promoter of interferon regulatory factor 1 (IRF1) or programmed death-ligand 1 (PD-L1), leading to their demethylation and downstream increase in PD-L1 expression [153,154].