The combination of anti-CTLA-4 and anti-PD(L)-1 is appealing for two reasons: (i) a biological rationale suggesting a synergy between anti-CTLA-4 (activating the T cells in the lymph node) and anti-PD(L)-1 (activating the T cells in the tumor site); and (ii) the successful ipilimumab/nivolumab association in melanoma [115] and in NSCLCC TMB high patients [107]. The gene discussed is CD274; the disease is melanoma.