Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles
Abstract Extracellular vesicles (EVs)-mediated communication by cancer cells contributes towards the pro-tumoral reprogramming of the tumor microenvironment. Viral infection has been observed to alter the biogenesis and cargo of EVs secreted from host cells in the context of infectious biology. Howe...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82331-9 |
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| author | Darshak K. Bhatt Annemarie Boerma Silvina Odete Bustos Andréia Hanada Otake Alexis Germán Murillo Carrasco Patrícia Pintor Reis Roger Chammas Toos Daemen Luciana Nogueira de Sousa Andrade |
| author_facet | Darshak K. Bhatt Annemarie Boerma Silvina Odete Bustos Andréia Hanada Otake Alexis Germán Murillo Carrasco Patrícia Pintor Reis Roger Chammas Toos Daemen Luciana Nogueira de Sousa Andrade |
| author_sort | Darshak K. Bhatt |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs)-mediated communication by cancer cells contributes towards the pro-tumoral reprogramming of the tumor microenvironment. Viral infection has been observed to alter the biogenesis and cargo of EVs secreted from host cells in the context of infectious biology. However, the impact of oncolytic viruses on the cargo and function of EVs released by cancer cells remains unknown. Here we show that upon oncolytic virotherapy with Semliki Forest virus-based replicon particles (rSFV), metastatic melanoma cells release EVs with a distinct biochemical profile and do not lead to suppression of immune cells. Specifically, we demonstrate that viral infection causes a differential loading of regulatory microRNAs (miRNAs) in EVs in addition to changes in their physical features. EVs derived from cancer cells potentially suppress splenocyte proliferation and induce regulatory macrophages. In contrast, EVs obtained from rSFV-infected cells did not exhibit such effects. Our results thus show that rSFV infection induces changes in the immunomodulatory properties of melanoma EVs, which may contribute to enhancing the therapeutic efficacy of virotherapy. Finally, our results show that the use of an oncolytic virus capable of a single-round of infection allows the analysis of EVs secreted from infected cells while preventing interference from extracellular virus particles. |
| format | Article |
| id | doaj-art-77b3aee7bd0043dc910d82b05e2f6d07 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-77b3aee7bd0043dc910d82b05e2f6d072025-01-05T12:14:28ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-82331-9Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesiclesDarshak K. Bhatt0Annemarie Boerma1Silvina Odete Bustos2Andréia Hanada Otake3Alexis Germán Murillo Carrasco4Patrícia Pintor Reis5Roger Chammas6Toos Daemen7Luciana Nogueira de Sousa Andrade8Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of GroningenDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of GroningenCenter for Translational Research in Oncology (LIM/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloCenter for Translational Research in Oncology (LIM/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloCenter for Translational Research in Oncology (LIM/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloDepartment of Surgery and Orthopedics and Experimental Research Unity (UNIPEX), Faculdade de Medicina, Universidade Estadual Paulista (UNESP)Center for Translational Research in Oncology (LIM/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of GroningenCenter for Translational Research in Oncology (LIM/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloAbstract Extracellular vesicles (EVs)-mediated communication by cancer cells contributes towards the pro-tumoral reprogramming of the tumor microenvironment. Viral infection has been observed to alter the biogenesis and cargo of EVs secreted from host cells in the context of infectious biology. However, the impact of oncolytic viruses on the cargo and function of EVs released by cancer cells remains unknown. Here we show that upon oncolytic virotherapy with Semliki Forest virus-based replicon particles (rSFV), metastatic melanoma cells release EVs with a distinct biochemical profile and do not lead to suppression of immune cells. Specifically, we demonstrate that viral infection causes a differential loading of regulatory microRNAs (miRNAs) in EVs in addition to changes in their physical features. EVs derived from cancer cells potentially suppress splenocyte proliferation and induce regulatory macrophages. In contrast, EVs obtained from rSFV-infected cells did not exhibit such effects. Our results thus show that rSFV infection induces changes in the immunomodulatory properties of melanoma EVs, which may contribute to enhancing the therapeutic efficacy of virotherapy. Finally, our results show that the use of an oncolytic virus capable of a single-round of infection allows the analysis of EVs secreted from infected cells while preventing interference from extracellular virus particles.https://doi.org/10.1038/s41598-024-82331-9Extracellular vesiclesOncolytic virusImmunomodulatoryMelanoma |
| spellingShingle | Darshak K. Bhatt Annemarie Boerma Silvina Odete Bustos Andréia Hanada Otake Alexis Germán Murillo Carrasco Patrícia Pintor Reis Roger Chammas Toos Daemen Luciana Nogueira de Sousa Andrade Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles Scientific Reports Extracellular vesicles Oncolytic virus Immunomodulatory Melanoma |
| title | Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles |
| title_full | Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles |
| title_fullStr | Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles |
| title_full_unstemmed | Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles |
| title_short | Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles |
| title_sort | oncolytic alphavirus induced extracellular vesicles counteract the immunosuppressive effect of melanoma derived extracellular vesicles |
| topic | Extracellular vesicles Oncolytic virus Immunomodulatory Melanoma |
| url | https://doi.org/10.1038/s41598-024-82331-9 |
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