Introduction: Extracellular vesicles (EVs) play a critical role in shaping the tumor immune microenvironment (TME) by mediating intercellular communication and transferring oncogenic proteins, microRNAs, and immunosuppressive molecules. Tumor-derived EVs (TDEVs) typically promote immune evasion by inducing M2 macrophage polarization, suppressing cytotoxic T-cell activity, and enhancing angiogenesis. Recent evidence suggests that oncolytic viruses (OVs) can reprogram EV secretion, generating OV-derived EVs (OV-EVs) with immunostimulatory properties capable of activating antitumor immune responses. Methods: In this study, we investigated how infection with oncolytic vaccinia virus (OVV) alters the EV secretion profile of colon cancer cells. EVs derived from OVV-infected tumor cells were isolated and characterized, and their effects on macrophage polarization were evaluated using in vitro assays. Results: Our results demonstrate that OVV infection significantly alters the composition and immunological properties of tumor-derived EVs. OV-EVs were enriched with pathogen-associated and damage-associated molecular patterns (PAMPs/DAMPs), which promoted macrophage reprogramming toward a pro-inflammatory M1 phenotype and enhanced immune activation associated with antitumor responses. Discussion: These findings indicate that OVV-induced EVs can reshape the tumor immune microenvironment by modulating macrophage polarization. This study provides new insights into the EV-mediated mechanisms of oncolytic virotherapy and highlights the potential of OV-derived EVs as a novel strategy for EV-based cancer immunotherapy. Keywords: extracellular vesicles, tumor immune microenvironment, oncolytic viruses, macrophage polarization
Chen et al. (Wed,) studied this question.