**10. Failure of tumor cells to activate immune system**

Tumors can also prevent the activation of the immune system by decreasing the expression of type I and II histocompatibility molecules [27]. The expression of co-inhibitory molecules, such as CD73 and programmed death ligand-1 (PD-L1) allows tumors to evade the immune system. The programmed cell death protein-1/ programmed death ligand-1 (PD-1/PD-L1) pathway promotes apoptosis of CD8+ T lymphocytes [35]. Whereas cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a co-inhibitor expressed by T cells that negatively regulates the activation of T cells. Therefore, the tumor can avoid the immune system because the immune cells are unable to recognize neoplastic cells either by apoptosis or exhaustion mechanisms. Many studies have focused on these pathways to inhibit tumor cells, and thus, restore the recognition and activation of the immune system.
