Immune tolerance that characterizes the evolution of HCC is regulated by innate and adaptive immune cells present in the immune tumor microenvironment (TME) such as CD4+ and CD8+ T-cells, dendritic cells (DCs), natural killer (NK) cells, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAMs) that express and up-regulate immune checkpoints on their surface as programmed cell death protein 1 (PD-1) and the cytotoxic lymphocyte protein 4 (CTLA-4) [18]. The gene discussed is PDCD1; the disease is hepatocellular carcinoma.