CD274 and melanoma: A 2010 study of individuals initially treated for metastatic melanoma which allowed enrollment of patients with treated CNS metastases was the first study to establish ipilimumab treatment improved survival.58 In addition, pembrolizumab and nivolumab have been clinically assessed for efficacy in patients with melanoma and lung cancer brain metastasis.59 Increased PD-L1 and CTLA-4 expression are indicative of therapeutic efficacy.