These findings can have important therapeutic implications as they suggest 1) a new mechanism of action of Ipilimumab; indeed, although formerly regarded as a CTLA-4 antagonist antibody for T cells, it can trigger a direct effect on melanoma tumor by inducing activation of cytolytic effector cells; ii) the possibility that different CTLA-4 levels on melanoma tissues could contribute to the heterogeneous patterns of clinical response that characterize the CTLA-4 immunotherapy in metastatic melanoma patients. The gene discussed is CTLA4; the disease is melanoma.