Here, we extend our previous findings by using hFcγR mice and chimeric anti-mCTLA-4 mAbs with human IgG variants to model the rules of engagement for human FcγRs and human IgGs in the context of immune modulatory mAbs, demonstrating that anti-human CTLA-4 mAbs work, at least in part, through depletion of tumor-infiltrating Treg cells. The gene discussed is CTLA4; the disease is neoplasm.