PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma

In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HiF alpha express elevated levels of PD-L1. in vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2 alpha, but not of HIF1 alpha, lead to reduced PD-L1 expression. The strong correlation of expression between the HIF2 alpha-specific HIF target Glut1 and PD-L1 confirmed this finding in ccRCC cell lines and tissue. Soluble PD-L1 levels remained constant in the sera of ccRCC patients regardless of the PD-L1 expression status in their tumors. In conclusion, our data suggest PD-L1 as HIF2 alpha target, which is upregulated in pVHL deficient ccRCC. The combination of PD-L1 targeting drugs with HIF inhibiting agents may be an addittonal op ion for the treatment of ccRCC.