Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV
We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1747 |
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| author | Tatiana Gianni Valerio Leoni Mara Sanapo Federico Parenti Daniela Bressanin Catia Barboni Anna Zaghini Gabriella Campadelli-Fiume Andrea Vannini |
| author_facet | Tatiana Gianni Valerio Leoni Mara Sanapo Federico Parenti Daniela Bressanin Catia Barboni Anna Zaghini Gabriella Campadelli-Fiume Andrea Vannini |
| author_sort | Tatiana Gianni |
| collection | DOAJ |
| description | We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, <i>Ido1</i> (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; <i>Cd40</i> and <i>Cd27</i> co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely. |
| first_indexed | 2024-03-10T07:09:00Z |
| format | Article |
| id | doaj.art-c2e0cfeece034633a0c106f8b9668105 |
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| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:09:00Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c2e0cfeece034633a0c106f8b96681052023-11-22T15:37:23ZengMDPI AGViruses1999-49152021-09-01139174710.3390/v13091747Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSVTatiana Gianni0Valerio Leoni1Mara Sanapo2Federico Parenti3Daniela Bressanin4Catia Barboni5Anna Zaghini6Gabriella Campadelli-Fiume7Andrea Vannini8Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, ItalyWe report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, <i>Ido1</i> (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; <i>Cd40</i> and <i>Cd27</i> co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.https://www.mdpi.com/1999-4915/13/9/1747oncolytic virusoncolytic herpes simplex virusretargetingHER2tumor genotypevaccination |
| spellingShingle | Tatiana Gianni Valerio Leoni Mara Sanapo Federico Parenti Daniela Bressanin Catia Barboni Anna Zaghini Gabriella Campadelli-Fiume Andrea Vannini Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV Viruses oncolytic virus oncolytic herpes simplex virus retargeting HER2 tumor genotype vaccination |
| title | Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV |
| title_full | Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV |
| title_fullStr | Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV |
| title_full_unstemmed | Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV |
| title_short | Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV |
| title_sort | genotype of immunologically hot or cold tumors determines the antitumor immune response and efficacy by fully virulent retargeted ohsv |
| topic | oncolytic virus oncolytic herpes simplex virus retargeting HER2 tumor genotype vaccination |
| url | https://www.mdpi.com/1999-4915/13/9/1747 |
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