This downregulation effect was observed with both pembrolizumab and nivolumab classical blocking anti-PD-1 mAbs currently marketed for cancer immunotherapy as well as a novel anti-PD-1 antibody the we previously reported that relieves functional T cell exhaustion through a mechanism that does not require the blockade of PD-1 with its cognate ligands (15, 41). This evidence concerns the gene PDCD1 and cancer.