CTLA4 and cancer: The mechanisms of CTLA-4-mediated immunosuppression in cancers are distinct from PD-1 and potentially synergistic with PD-1 (46): although both receptors act on activated conventional T cells, PD-1 controls effector T-cell function at a later stage, mainly within peripheral tissue sites and the tumor microenvironment, while CTLA-4 intercepts T-cell priming in the lymph nodes and governs the function of Tregs (47, 48).