On the other hand, recent studies suggest that rather than blocking the B7-CTLA-4 interaction, the therapeutic effect of anti-mouse CTLA-4 mAbs requires antibody-mediated depletion of regulatory T cells (Tregs) specifically within tumor microenvironment.16–18 These studies raise the intriguing possibility that CITE can be achieved without irAE if one can achieve local Treg cell depletion without mimicking genetic inactivation of CTLA-4 expression. This evidence concerns the gene CTLA4 and neoplasm.