CD4 and neoplasm: Recent animal studies with anti-CTLA-4 mAb using mice lacking antibody-dependent cytotoxic activity (by modulation of the Fc fraction or Fc receptor knockdown) showed that the anti-CTLA-4 mAb antitumor activity was attributed to depletion of FOXP3+CD4+ Treg cells from tumor tissue rather than direct activation of effector T cells (Bulliard et al., 2013; Selby et al., 2013; Simpson et al., 2013).