[36] CTLA4 manifold control of tolerance is complex and involves competition with co-stimulatory molecules, dysregulation of the immunological synapse, inhibition of inflammatory cytokines, and preservation of CD4+ TREG cell function. [37] Therapies with anti-CTLA4 blocking antibodies have some modest benefit in cancer patients. [38], [39] Taken together with our data, these studies suggest that suppressing CTLA4 signaling may be necessary but not sufficient for robust clinical response in cancer patients. The gene discussed is CTLA4; the disease is cancer.