Nasopharyngeal cancer cell-derived exosomal PD-L1 inhibits CD8+ T-cell activity and promotes immune escape.
Nasopharyngeal cancer cell-derived exosomal PD-L1 inhibits CD8+ T-cell activity and promotes immune escape.
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鼻咽癌细胞来源的外泌体PD-L1抑制CD 8 + T细胞活性并促进免疫逃逸
作者：
程序性细胞死亡配体1（PD-L1）是一种免疫表面蛋白，与程序性细胞死亡1（PD-1）结合，使肿瘤逃避T细胞免疫。本研究旨在确定肿瘤细胞源性外泌体穿梭的PD-L1在鼻咽癌（NPC）免疫逃逸中的作用。在从NPC患者的血浆或从NPC细胞分离的外泌体中测定PD-L1表达。发现PD-L1在来自NPC患者血浆的外泌体中以及在来自NPC细胞的外泌体中高度表达。在存在或不存在干扰素-γ（IFN-γ）或抗-PD-L1抗体的情况下鉴定PD-L1/PD-1结合。IFN-γ治疗后PD-L1表达升高。IFN-γ增强了PD-L1与PD-1的结合，并被抗PD-L1抗体阻断。此后，从外周血样品中分选出CD 8 + T细胞，以评估外泌体PD-L1和CD 8 + T细胞表面上的PD-1之间的结合，并测量Ki-67阳性T细胞的百分比。结果表明，外泌体PD-L1与CD 8 + T细胞表面的PD-1结合，导致Ki-67阳性CD 8 + T细胞的百分比降低，细胞因子的产生下调。体内数据证实，外泌体PD-L1通过抑制CD 8 + T细胞活性促进小鼠NPC肿瘤生长。总之，NPC细胞来源的外泌体递送PD-L1以结合CD 8 + T细胞表面上的PD-1，通过其减弱细胞毒性CD 8 + T细胞功能，从而促进NPC中的免疫逃逸。鼻咽癌（NPC）细胞来源的外泌体递送程序性细胞死亡配体1以结合CD 8 + T细胞表面上的程序性细胞死亡1，通过其减弱细胞毒性CD 8 + T细胞功能，从而促进NPC中的免疫逃逸。
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. Nasopharyngeal carcinoma (NPC) cell‐derived exosomes deliver programmed cell death ligand 1 to bind to programmed cell death 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.
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DOI：
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