A schematic summary of our study results showing a pivotal role that ipilimumab may play in modulating T cell and NK/NKT cell activation. (a) CTLA-4 on the surface of Treg or early activated T cells competes with CD28 in binding with co-stimulatory factors CD80 or CD86 on antigen presenting cells. (b) Ipilimumab enhances proliferation of CD8+ T cells while proliferation of CD4+ T cells was reduced, hence the decreased CD4/CD8 ratio. The enhanced CD8+ T cell proliferation resulted in the improved BiAb-mediated antitumor cytotoxicity in both Daudi and COLO356/FG models. The enhanced antitumor activity was consistently observed in elevated secretion of IFN-γ and decreased IL-10 secretion. Although there was no difference between control and ipilimumab groups in NKT cell proliferation, ipilimumab-mediated NKT cell activation may have contributed in the increased cytotoxicity and IFN-γ secretion.