Moreover, use of ipilimumab (CTLA-4 antibody) depleted CTLA-4+ melanoma cell lines through antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro and in a mouse model [16], which implies that CTLA-4 blockade could both reverse immunosuppression in tumor microenvironment and destroy CTLA-4+ tumor cells directly through ADCC. This evidence concerns the gene CTLA4 and melanoma.