The immune system has checkpoint ligands that protect an organism against an excessive inflammatory response to viral or bacterial infection. Tumors co-opt this mechanism to evade immune cells. For example, tumor cells expressing programmed death ligand-1 (PD-L1) promote T-cell exhaustion, where T cells proliferate slowly and do not function effectively. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression on tumors can upregulate regulatory T cells which inhibit effector T cells. There are many distinct checkpoint pathways and thus many inhibitors that can be rationally combined.