CD274 and metastatic melanoma: In metastatic melanoma patients, the amount of circulating EVs-PD-L1 is positively associated with that of IFN-γ, and differs following anti-PD-1 therapy [62], Inhibiting the cystine/glutamate transporter cystine-glutamate exchange resulted in higher PD-L1 levels in melanoma and increased EVs-PD-L1 secretion, which in turn induced M2 macrophage polarization and prevented the efficiency of anti-PD-1/PD-L1 therapy in melanoma [63].