The mechanism of action of anti–CTLA-4 mAb has also been disputed, particularly in cancer biology, with multiple studies now suggesting that the antitumor effects of some anti–CTLA-4 mAb variants primarily result from Ab-mediated depletion of CTLA-4–expressing Treg (82–84), which in effect predominantly depletes intratumoral eTreg given their high expression of CTLA-4 (27–29). This evidence concerns the gene CTLA4 and cancer.