In preclinical studies in murine cancer models, anti-CTLA-4 monoclonal antibodies were initially thought to act simply via blocking CTLA-4 on effector T cells and Tregs [10], but subsequent studies demonstrated that the activity of anti-CTLA-4 antibodies may extend beyond CTLA-4 blockade of effector T cells and Tregs, relying upon concomitant depletion of Tregs for maximal anti-tumor activity. The gene discussed is CTLA4; the disease is cancer.