Nasopharyngeal cancer cell-derived exosomal PD-L1 inhibits CD8+ T-cell activity and promotes immune escape

Abstract

Programmed cell death ligand 1 (PD-L1) is an immune surface protein that binds to programmed cell death 1 (PD-1) and allows tumors to evade T-cell immunity. This study aims to define the role of PD-L1 shuttled by tumor cell-derived exosomes in the immune escape of nasopharyngeal carcinoma (NPC). PD-L1 expression was determined in the exosomes isolated from the plasma of NPC patients or from NPC cells. It was found that PD-L1 was highly expressed in the exosomes from the plasma of NPC patients and also in the exosomes from NPC cells. PD-L1/PD-1 binding was identified in the presence or absence of interferon-gamma (IFN-γ) or anti-PD-L1 antibody. PD-L1 expression was elevated following IFN-γ treatment. Binding of PD-L1 to PD-1 was augmented by IFN-γ and blocked by anti-PD-L1 antibody. Following this, CD8+ T cells were sorted out from peripheral blood samples to assess the binding between exosomal PD-L1 and PD-1 on the CD8+ T-cell surface, and to measure the percentage of Ki-67-positive T cells. The results indicated that exosomal PD-L1 bound to the PD-1 on CD8+ T-cell surface, leading to a reduced percentage of Ki-67-positive CD8+ T cells and downregulated production of cytokines. In vivo data confirmed that exosomal PD-L1 promoted NPC tumor growth in mice by suppressing CD8+ T-cell activity. In conclusion, NPC cell-derived exosomes deliver PD-L1 to bind to PD-1 on the CD8+ T-cell surface, through which cytotoxic CD8+ T-cell function was attenuated and the immune escape was thus promoted in NPC.

Keywords: CD8+ T cells; IFN-γ; exosomes; immune escape; nasopharyngeal carcinoma; programmed cell death ligand 1; programmed cell death-1.