In cancer, the interactions between PD-1 on cytotoxic T-lymphocytes and PD-L1 on tumor cells or tumor macrophages, NK cells, dendritic cells, and various other immune cells, result in an exhausted T-cell phenotype, rendering the immune system unable to detect and eliminate tumors via epigenetic changes within T-cells (Figure 3) [168,171,174,175,176,177,178,179,180,181,182]. This evidence concerns the gene PDCD1 and cancer.