Here we found that Hypoxia/HIF-1α, beside controlling PD-L1 expression on tumor cells by directly binding to the HRE motif in the promoter of PD-L1 gene [12], promotes PD-1 expression in T cells through a mechanism involving the upregulation of the cytosolic adaptor Rai, which our data identify as a novel HIF-1α target gene. Here, SHC3 is linked to neoplasm.