Having previously identified the soluble isoform of CTLA-4 as a candidate regulatory molecule capable of suppressing antigen specific effector T cell responses (36), we demonstrate here for the first time a novel mechanism based specifically on the TGFβ2 isoform that drives sCTLA-4 to be produced at high levels in human patients with melanoma and which we propose is used as a tumor immune evasion strategy. The gene discussed is CTLA4; the disease is neoplasm.