放射治疗是目前鼻咽癌的主要治疗手段，但PD-L1高表达的患者放疗后预后不佳，此类患者仍需新的综合治疗方法。PD-L1可被外泌体包裹并传递至T细胞，从而发挥免疫抑制效应。前期研究发现，PD-L1与患者不良预后呈正相关并与HIF-1α共定位，其表达受EB病毒编码的潜伏膜蛋白1（LMP1）及HIF-1α调控；且鼻咽癌患者血浆中PD-L1+外泌体数量显著高于正常人。我们因此推断，PD-L1+外泌体可介导鼻咽癌的免疫逃逸，而LMP1/HIF-1α参与鼻咽癌细胞及外泌体中PD-L1功能的活化。本研究拟分析鼻咽癌循环血浆PD-L1+外泌体的免疫抑制效应及其与放疗后患者预后的关系，进行体内外实验阐明LMP1/HIF-1α调控鼻咽癌细胞及外泌体中PD-L1的作用机制，为鼻咽癌免疫治疗提供新的思路。

Currently, radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, NPC patients with upregulated Programmed Death-Ligand 1 (PD-L1) exhibit a poor prognosis after radiotherapy. Therefore, novel integrating treatment is urgently needed for these patients. PD-L1 has been reported to be carried by exosomes and transported to T cells, leading to immune suppression effects. Previous studies indicate a significant correlation between PD-L1 and prognosis of NPC patients. Furthermore, PD-L1 is co-located with HIF-1α in NPC tissues and expression of PD-L1 is regulated by Latent Membrane Protein 1 (LMP1), an important oncogene encoded by Epstein-Barr virus, and HIF-1α. Moreover, exosomes with PD-L1 positive (PD-L1+) were significantly induced in plasma of NPC patients than the control group. Thus, we hypothesize that PD-L1+ exosomes could mediate potent immune suppression and function of PD-L1 may be activated by LMP1/HIF-1α in NPC cells and tumor-derived exosomes. The aim of the study is to isolate and identify plasma exosomes to investigate the correlation between PD-L1+ exosomes in plasma and the prognosis of NPC patients after radiotherapy; to analyze the immune suppression effects of PD-L1+ exosomes to T cell immune response; to clarify the mechanism of LMP-1/HIF-1α in regulating function of PD-L1 in NPC cells and in tumor-derived exosomes in vitro and in vivo. The accomplishment of this study could provide novel insights for NPC immunotherapy.