Negative checkpoint regulators, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3), have been successfully targeted in several cancers.1, 2, 3, 4 However, existing checkpoint inhibitors targeting these negative regulators are effective in only a small portion of patients and even among responders, some relapse.5 The gene discussed is CD274; the disease is cancer.