Oncolytic alphavirus replicons mediated recruitment and activation of T cells
Summary: Oncolytic viruses show promise in enhancing tumor immunogenicity by releasing immunogenic signals during tumor cell infection and lysis. In this study, we improved the virus-induced tumor immunogenicity of recombinant Semliki Forest virus (rSFV)-based replicon particles by encoding immunoge...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224004747 |
| _version_ | 1797295214583349248 |
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| author | Darshak K. Bhatt Saskia L. Meuleman Baukje Nynke Hoogeboom Toos Daemen |
| author_facet | Darshak K. Bhatt Saskia L. Meuleman Baukje Nynke Hoogeboom Toos Daemen |
| author_sort | Darshak K. Bhatt |
| collection | DOAJ |
| description | Summary: Oncolytic viruses show promise in enhancing tumor immunogenicity by releasing immunogenic signals during tumor cell infection and lysis. In this study, we improved the virus-induced tumor immunogenicity of recombinant Semliki Forest virus (rSFV)-based replicon particles by encoding immunogenic cytokines such as C-X-C motif chemokine ligand 10 (CXCL10), FMS-like tyrosine kinase 3 ligand (Flt3L), or interferon-gamma (IFN-ƴ). Real-time imaging and flow cytometry of human cancer cell-based monolayer and spheroid cultures, using LNCaP or PANC-1 cells, revealed effective infection and transgene expression in both models. LNCaP cells exhibited higher and earlier rSFV infection compared to PANC-1 cells. While infected LNCaP cells effectively triggered immune recruitment and T cell activation even without encoding cytokines, PANC-1 cells demonstrated improved immune responses only when infected with replicons encoding cytokines, particularly IFN-ƴ, which enhanced tumor immunogenicity irrespective of cancer cell susceptibility to infection. Our study demonstrates that despite innate phenotypic disparities in cancer cells, rSFV-based replicons encoding cytokines can potentially generate effective immune responses in the tumor. |
| first_indexed | 2024-03-07T21:43:32Z |
| format | Article |
| id | doaj.art-6facd2f6931f4ad8a9a3e61b629a3d1e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-07T21:43:32Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6facd2f6931f4ad8a9a3e61b629a3d1e2024-02-26T04:16:10ZengElsevieriScience2589-00422024-03-01273109253Oncolytic alphavirus replicons mediated recruitment and activation of T cellsDarshak K. Bhatt0Saskia L. Meuleman1Baukje Nynke Hoogeboom2Toos Daemen3Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands; Corresponding authorSummary: Oncolytic viruses show promise in enhancing tumor immunogenicity by releasing immunogenic signals during tumor cell infection and lysis. In this study, we improved the virus-induced tumor immunogenicity of recombinant Semliki Forest virus (rSFV)-based replicon particles by encoding immunogenic cytokines such as C-X-C motif chemokine ligand 10 (CXCL10), FMS-like tyrosine kinase 3 ligand (Flt3L), or interferon-gamma (IFN-ƴ). Real-time imaging and flow cytometry of human cancer cell-based monolayer and spheroid cultures, using LNCaP or PANC-1 cells, revealed effective infection and transgene expression in both models. LNCaP cells exhibited higher and earlier rSFV infection compared to PANC-1 cells. While infected LNCaP cells effectively triggered immune recruitment and T cell activation even without encoding cytokines, PANC-1 cells demonstrated improved immune responses only when infected with replicons encoding cytokines, particularly IFN-ƴ, which enhanced tumor immunogenicity irrespective of cancer cell susceptibility to infection. Our study demonstrates that despite innate phenotypic disparities in cancer cells, rSFV-based replicons encoding cytokines can potentially generate effective immune responses in the tumor.http://www.sciencedirect.com/science/article/pii/S2589004224004747ImmunologyVirology |
| spellingShingle | Darshak K. Bhatt Saskia L. Meuleman Baukje Nynke Hoogeboom Toos Daemen Oncolytic alphavirus replicons mediated recruitment and activation of T cells iScience Immunology Virology |
| title | Oncolytic alphavirus replicons mediated recruitment and activation of T cells |
| title_full | Oncolytic alphavirus replicons mediated recruitment and activation of T cells |
| title_fullStr | Oncolytic alphavirus replicons mediated recruitment and activation of T cells |
| title_full_unstemmed | Oncolytic alphavirus replicons mediated recruitment and activation of T cells |
| title_short | Oncolytic alphavirus replicons mediated recruitment and activation of T cells |
| title_sort | oncolytic alphavirus replicons mediated recruitment and activation of t cells |
| topic | Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224004747 |
| work_keys_str_mv | AT darshakkbhatt oncolyticalphavirusrepliconsmediatedrecruitmentandactivationoftcells AT saskialmeuleman oncolyticalphavirusrepliconsmediatedrecruitmentandactivationoftcells AT baukjenynkehoogeboom oncolyticalphavirusrepliconsmediatedrecruitmentandactivationoftcells AT toosdaemen oncolyticalphavirusrepliconsmediatedrecruitmentandactivationoftcells |