CD274 and melanoma: They showed that inhibition of xCT blunted the efficacy of PD-1/PD-L1 blockade through upregulating PD-L1 expression via the transcription factors IRF4/EGR1, and thus exosomes carrying large amounts of PD-L1 secreted from melanoma cells induced macrophage M2 polarization and eventually induced anti-PD-1/PD-L1 therapy resistance (127).