Oncolytic viruses alter the biogenesis of tumor extracellular vesicles and influence their immunogenicity
Extracellular vesicles (EVs) are mediators of intercellular communication in the tumor microenvironment. Tumor EVs are commonly associated with metastasis, immunosuppression or drug resistance. Viral infections usually increase EV secretion, but little is known about the effect of oncolytic viruses (OVs) on tumor EVs. Here, we investigated the impact of oncolytic vesicular stomatitis virus (VSV) and vaccinia virus on EVs secreted by human melanoma and thoracic cancer cells. We found that OV infection increases the production of EVs by tumor cells. These EVs contain proteins of viral origin, such as VSV-G, thus creating a continuum of particles sharing markers of both canonical EVs and viruses. As such, the presence of VSV-G on EVs improves the transfer of their protein content to cell types commonly found in the tumor microenvironment. A proteomic analysis also revealed that EVs-OV secreted during VSV infection are enriched in immunity-related proteins. Finally, CD8<sup>+</sup> T cells incubated with EVs-OV from infected cells display slightly enhanced cytotoxic functions. Taken together, these data suggest that OVs enhance the communication mediated by tumor EVs, which could participate in the therapeutic efficacy of OVs. These results also provide rationale for engineering OVs to exploit EVs and disseminate therapeutic proteins within the tumor microenvironment.
Authors
- Jean‐François Fonteneau (ORCID: https://orcid.org/0000-0002-3284-8319)
- Nicolas Boisgerault (ORCID: https://orcid.org/0000-0002-3391-6504)
- Charles Pineau (ORCID: https://orcid.org/0000-0002-7461-5433)
- Emmanuelle Com (ORCID: https://orcid.org/0000-0002-7401-817X)
- Morgane Fouet (ORCID: https://orcid.org/0000-0002-1764-1432)
- Philippe Erbs (ORCID: https://orcid.org/0000-0002-6810-4610)
- Nathalie Labarrière (ORCID: https://orcid.org/0000-0002-1407-6546)
- Morgane Krejbich
- Judith Fresquet
- Julien Burlaud‐Gaillard (ORCID: https://orcid.org/0000-0001-5171-9873)
- Tacien Petithomme (ORCID: https://orcid.org/0000-0002-8609-1331)
- Delphine Fradin (ORCID: https://orcid.org/0000-0001-6231-2649)
- Bastien Arnaud (ORCID: https://orcid.org/0000-0001-6210-1649)
- Ugo Hirigoyen (ORCID: https://orcid.org/0000-0001-6279-7367)
- Gwenann Cadiou
- Coraly Guilbaud
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Transgene (France) (FR)
- Inserm (FR)
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Institut de Recherche en Santé, Environnement et Travail (FR)
- Structure Fédérative de Recherche en Biologie et Santé de Rennes (FR)
- Université de Rennes (FR)
- Nantes Université (FR)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1016/j.omton.2024.200887
- Citations
- 10
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 5.50
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Conseil Régional de Bretagne
- Centre National de la Recherche Scientifique