Targeting signaling molecules to enhance anti-cancer immunity has focused on two approaches: (a) activating costimulatory molecules with agonistic Abs directed to T cell surface molecules- CD27, CD40, OX40 and CD137; or (b) blockade of inhibitory pathways with monoclonal Abs directed to cell surface CTLA-4, PD-1/PD-L1, TIM-3, BTLA and LAG-3 [32]. The gene discussed is TNFRSF4; the disease is cancer.