Inhibition of the cystine/glutamate transporter xCT by sulfasalazine (SAS) or genetic knockdown induces ROS-related death in melanoma cells but simultaneously reduces the efficacy of anti-PD-1/PD-L1 therapy by upregulating PD-L1 expression via IRF4/EGR1 transcription factors, leading to exosome-mediated M2 macrophage polarization and subsequent resistance to the immune checkpoint blockade (108). Here, CD274 is linked to melanoma.