During chronic viral infection and cancer, tumor antigen–specific (TA-specific) CD8+ T cells become dysfunctional and upregulate multiple inhibitory receptors, including programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte–associated antigen 4 (CTLA-4; refs. 1, 2). The gene discussed is CD274; the disease is neoplasm.