The negative co-stimulatory molecules CTLA-4 and PD-L1/PD-1 are critical mediators of tumor-mediated immune suppression and tolerance, and antibodies that block their function have become a major new area of cancer therapeutics.22,90 Blockade of CTLA-4 has demonstrated activity via activation of cell-mediated immunity and has received approval by the FDA for patients with recurrent melanoma. Here, CTLA4 is linked to cancer.