细胞外囊泡（EVs）的循环性质使其能够将载荷传递给邻近或远离的细胞，从而成为细胞间通信的重要介质。已发现EB病毒（EBV）感染的细胞会释放包含病毒蛋白的EVs，例如主要病毒致癌基因潜伏膜蛋白1（LMP1）。已观察到LMP1调节细胞基因表达的程序性细胞死亡蛋白1配体（PD-L1），该蛋白通过与细胞毒性T细胞上的受体结合来抑制免疫系统。最近的研究表明，PD-L1包装入小型EVs（sEVs）中，可能有助于肺癌细胞逃避免疫系统。此外，已观察到肿瘤细胞大量产生大型EVs（lEVs），并且增加的lEVs水平与疾病转移和癌症侵袭性相关。本研究证明鼻咽癌细胞的lEVs中具有明显富集的PD-L1。此外，发现EBV蛋白LMP1在调节这些lEVs中的PD-L1水平中起关键作用。这些含有LMP1的PD-L1+ lEVs可能有助于EBV相关癌症中免疫抑制的微环境。重要性日益增长的证据支持病毒利用EVs和相关途径来包含病毒产物的观点。这允许免疫反应逃避，并在宿主内实现病毒传播。鉴于病毒蛋白通常引发强烈的由T细胞识别的抗原肽，通过过表达lEV相关的PD-L1调节PD-L1通路可能作为病毒免疫逃逸的策略。发现EBV LMP1增加在较大EVs中分泌的PD-L1，为EBV相关癌症免疫阻断治疗提供了一个新的潜在目标。我们的研究结果可能有助于阐明LMP1介导的PD-L1包装进lEVs的机制，并可能导致更具针对性的治疗靶点的发现。此外，识别能预测疾病病毒来源的lEV生物标志物可能有助于开发更加有针对性的治疗方法。

The circulating nature of extracellular vesicles (EVs) allows for the transfer of cargo to proximal or distant cells, making them vital mediators of cellular communication. Epstein-Barr virus (EBV)-infected cells have been found to release EVs containing viral proteins, such as the major viral oncogene latent membrane protein 1 (LMP1). LMP1 has been observed to regulate the cellular gene expression of the programmed cell death protein 1 ligand (PD-L1), a protein known to suppress the immune system through binding to a receptor found on cytotoxic T cells. Recent studies have established that PD-L1 is packaged into small EVs (sEVs), potentially contributing to the evasion of lung cancer cells from the immune system. Furthermore, it has been observed that large EVs (lEVs) are shed in significant quantities by tumor cells, with elevated levels of lEVs being associated with disease metastasis and cancer aggressiveness. The present study demonstrated that lEVs from nasopharyngeal carcinoma cells exhibit a significant enrichment of PD-L1. Furthermore, the EBV protein LMP1 was found to play a key role in regulating PD-L1 levels within these lEVs. These PD-L1+ lEVs containing LMP1 are likely to contribute to the immunosuppressive microenvironment found in EBV-associated cancers. IMPORTANCE A growing body of evidence has supported the notion that viruses utilize EVs and associated pathways to incorporate viral products. This allows for the evasion of an immune response while enabling viral spread within the host. Given that viral proteins often elicit strong antigenic peptides that are recognized by T cells, the regulation of the PD-L1 pathway through the overexpression of lEV-associated PD-L1 may serve as a strategy for immune evasion by viruses. The discovery that EBV LMP1 increases the secretion of PD-L1 in larger EVs identifies a new potential target for immune blockade therapy in EBV-associated cancers. Our findings may help to clarify the mechanism of LMP1-mediated enhancement of PD-L1 packaging into lEVs and may lead to the identification of more specific targets for treatment. Additionally, the identification of lEV biomarkers that predict a viral origin of disease could allow for more targeted therapies to be developed.