Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors

Model for the combination of vaccine-based therapy and immune checkpoint inhibitors. (A) Pancreatic ductal adenocarcinoma (PDA) is infiltrated primarily with M2 macrophages (M2), type 2 T helper cells (Th2), myeloid-derived suppressive cells (MDSC), and regulatory T cells (Treg) but with few effector T cells (Teffs). Lacking PD-1/PD-L1 targets, PDA does not respond to single-agent checkpoint inhibitor treatments, such as anti-PD-1 or PD-L1 therapeutic antibodies (anti-PD-1/PD-L1 Ab). (B) Following vaccine-based therapy, vaccine-induced Teffs are infiltrated into PDA; however, PD-L1/PD-L1-mediated immune checkpoint pathways are also induced. By targeting PD-L1/PD-L1 signals on PDA tumor cells and monocytes (Mo) induced by vaccine-based therapy, anti-PD-1/PD-L1 therapeutic antibodies enhance vaccine-induced antitumor immune responses.