CD274 and Epstein-Barr virus infection: Indeed, mechanisms leading to the PD-L1 upregulation by the HRS cells are due to several causes, mainly including genetic alterations to the PD-L1 and PDL2 locus of chromosome 9p24.1 (gains, amplifications or fusions), EBV infection that directly activates the PD-L1 promoter via the AP-1/cJUN/JUN-B pathway, and JAK-STAT signaling [4].