In the absence of malignancy, receptors CTLA-4, PD-1/PD-2, and PDL-1 reduce T-cell proinflammatory response and decrease tissue damage from the immune system, improving self-tolerance.2,11–13 When cancers develop, malignant cells upregulate these receptors, which decreases immune system clearance of these cells. The gene discussed is CD274; the disease is cancer.