Monoclonal antibodies targeting negative signaling receptors on immune cells - termed checkpoint inhibitors - to break tolerance on functionally exhausted tumor antigen-specific T cells have improved survival across multiple cancer types, as exemplified by the durable clinical responses seen in > 50% of patients with advanced melanoma treated with combination anti-PD-1 and anti-CTLA-4 therapy1. The gene discussed is CTLA4; the disease is neoplasm.