Engagement of PD-1 in T cells by PD-L1 during an immune response is bidirectional: on one hand, downregulated CD8 T cell functions induce “CD8 T cell exhaustion”, an anergic phenotype, and in the end apoptosis of tumor-specific T cells which express a high level of PD-1 [87,88] and on the other hand PD-L1 can deliver an anti-apoptotic signal in cancer cells that prevents apoptosis [30]. This evidence concerns the gene CD8A and cancer.