Given these findings as well as the supporting data suggesting that the loss of TβRIII in murine melanoma models also promotes the development of an immune suppressive microenvironment, we investigated the combination of another oral type I TGF-β receptor kinase inhibitor currently in clinical trial development, LY2157299 monohydrate (80, 81), with anti-CTLA-4 monoclonal antibody therapy in the Tyr:CreER;BrafCA;Ptenlox/lox transgenic melanoma mouse model (82). The gene discussed is CTLA4; the disease is melanoma.