,28,29,30,31,32 However, there is currently no definitive evidence that approved human anti-CTLA-4 antibodies (ipilimumab and tremelimumab) deplete intratumoral Tregs in patients with cancer,33,34 which is likely to be due to the isotype format of these antibodies that were initially selected for their ability to block CTLA-4 and not to deplete Tregs.22 The gene discussed is CTLA4; the disease is cancer.