A significant reduction in PD-L1 mRNA and protein levels in A375 and SK-MEL-28 melanoma cell lines in vitro, as well as effective suppression of B16-F10 melanoma lung metastases by combination therapy with checkpoint inhibitors (anti-PD-1 and/or anti-CTLA-4), has been shown in mouse models in vivo [131]. This evidence concerns the gene CTLA4 and melanoma.