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This article reports a novel mechanism by which Epstein-Barr virus (EBV) microRNA (miRNA) plays a role to fine-tune the expression of LMP1-driven amplification of inhibitory checkpoint programmed death ligand 1 (PD-L1) and PD-L2 in EBV+ diffuse large B-cell lymphoma. Identification and understanding of the immune checkpoint regulation via miRNA may enable potential novel RNA-based therapies to emerge.