Dissertation Defense: The Role of Epstein-Barr Virus LMP1 in Enhancing Levels of Large Extracellular Vesicle-Associated PD-L1: Implications for Immune Evasion and Cancer Progression
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. The study also identifies potential therapeutic targets for EBV-associated cancers, including the PD-L1 pathway and the use of peripheral blood mononuclear cells (PBMCs). These PD-L1+ lEVs containing LMP1 are likely to contribute to the immunosuppressive microenvironment found in EBV-associated cancers.
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