Extracellular vesicles released from Marek's disease virus-transformed T-cells impact immune cell proliferation

Marek's disease virus (MDV) is an alphaherpesvirus responsible for the development of T-cell lymphoma in chickens. Despite the identification of several pro-oncogenic viral molecules encoded by MDV, the processes leading to tumourigenesis remain poorly understood. Extracellular vesicles (EVs) are important mediators of intercellular communication, carrying bioactive molecules that can elicit profound physiological changes in recipient cells. Tumour cells can release significant amounts of EVs, which influence tumour development and growth, metastatic processes and resistance to cancer therapies. These EVs favour cancer cells to evade the immune response, particularly by establishing an immunosuppressive microenvironment. Here, we investigated whether EVs produced by MDV-transformed T lymphocytes affect the proliferation of avian immune cells, a determining feature in neoplastic processes. EVs were purified from an MDV-transformed cell line cultured in vitro. Using a proteomic approach, we confirmed the presence of specific markers and identified a panel of cellular proteins enriched in these EVs. Notably, no viral proteins were detected in the purified EVs. We also demonstrated that EVs are rapidly internalized by recipient chicken cells. Moreover, these EVs can induce a decrease in primary chicken B-cell proliferation, while promoting primary chicken T-cell proliferation. Our findings suggest that EVs released by MDV-transformed cells may contribute to immunosuppression and potentially facilitate lymphoma progression by enhancing T-cell proliferation.