Studies of immune cell exhaustion and tumor-infiltrating lymphocyte (TIL) dysfunction due to persistent antigenic stimuli (e.g., chronic viral infection and tumors) have revealed cell surface proteins that are involved in the functional impairment of immune cells; these proteins include multiple co-inhibitory or checkpoint receptors, such as cytotoxic T lymphocyte antigen-4 (CTLA-4, CD152), programmed death-1 (PD-1, CD279), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene (LAG-3)1. The gene discussed is PDCD1; the disease is neoplasm.