[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. Here, CD4 is linked to cancer.