Betting on improved cancer immunotherapy by doubling down on CD134 and CD137 co-stimulation.

摘要

The ability of T cells to recognize a vast array of antigens enables them todestroy tumor cells while inflicting minimal collateral damage. Nevertheless,tumor antigens often are a form of self-antigen, and thus tumor immunity can bedampened by tolerance mechanisms that evolved to prevent autoimmunity. Sincetolerance can be induced by steady-state antigen-presenting cells that provideinsufficient co-stimulation, the exogenous administration of co-stimulatoryagonists can favor the expansion and tumoricidal functions of tumor-specific Tcells. Agonists of the co-stimulatory tumor necrosis factor receptor (TNFR)family members CD134 and CD137 exert antitumor activity in mice, and asmonotherapies have exhibited encouraging results in clinical trials. This review focuses on how the dual administration of CD134 and CD137 agonistssynergistically boosts T-cell priming and elaborates a multi-pronged antitumorimmune response, as well as how such dual co-stimulation might be translated intoeffective anticancer therapies.