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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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Autores principales: Gianni, Tatiana, Leoni, Valerio, Sanapo, Mara, Parenti, Federico, Bressanin, Daniela, Barboni, Catia, Zaghini, Anna, Campadelli-Fiume, Gabriella, Vannini, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473155/
https://www.ncbi.nlm.nih.gov/pubmed/34578328
http://dx.doi.org/10.3390/v13091747
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author Gianni, Tatiana
Leoni, Valerio
Sanapo, Mara
Parenti, Federico
Bressanin, Daniela
Barboni, Catia
Zaghini, Anna
Campadelli-Fiume, Gabriella
Vannini, Andrea
author_facet Gianni, Tatiana
Leoni, Valerio
Sanapo, Mara
Parenti, Federico
Bressanin, Daniela
Barboni, Catia
Zaghini, Anna
Campadelli-Fiume, Gabriella
Vannini, Andrea
author_sort Gianni, Tatiana
collection PubMed
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, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 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.
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spelling pubmed-84731552021-09-28 Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV Gianni, Tatiana Leoni, Valerio Sanapo, Mara Parenti, Federico Bressanin, Daniela Barboni, Catia Zaghini, Anna Campadelli-Fiume, Gabriella Vannini, Andrea Viruses Article 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, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 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. MDPI 2021-09-01 /pmc/articles/PMC8473155/ /pubmed/34578328 http://dx.doi.org/10.3390/v13091747 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gianni, Tatiana
Leoni, Valerio
Sanapo, Mara
Parenti, Federico
Bressanin, Daniela
Barboni, Catia
Zaghini, Anna
Campadelli-Fiume, Gabriella
Vannini, Andrea
Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473155/
https://www.ncbi.nlm.nih.gov/pubmed/34578328
http://dx.doi.org/10.3390/v13091747
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