Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity
Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic her...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770516300043 |
| _version_ | 1828390575251914752 |
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| author | Jennifer L Leddon Chun-Yu Chen Mark A Currier Pin-Yi Wang Francesca A Jung Nicholas L Denton Kevin M Cripe Kellie B Haworth Michael A Arnold Amy C Gross Timothy D Eubank William F Goins Joseph C Glorioso Justus B Cohen Paola Grandi David A Hildeman Timothy P Cripe |
| author_facet | Jennifer L Leddon Chun-Yu Chen Mark A Currier Pin-Yi Wang Francesca A Jung Nicholas L Denton Kevin M Cripe Kellie B Haworth Michael A Arnold Amy C Gross Timothy D Eubank William F Goins Joseph C Glorioso Justus B Cohen Paola Grandi David A Hildeman Timothy P Cripe |
| author_sort | Jennifer L Leddon |
| collection | DOAJ |
| description | Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic herpes simplex virus replication and cytotoxicity in vitro, with the most permissive being comparable to some human sarcoma tumor lines. The in vivo antitumor effect ranged from no or modest response to complete tumor regression and protection from tumor rechallenge. The in vitro permissiveness to viral oncolysis was not predictive of the in vivo antitumor effect, as all three tumors showed intact interferon signaling and minimal permissiveness to virus in vivo. Tumor shrinkage was T-cell mediated with a tumor-specific antigen response required for maximal antitumor activity. Further analysis of the innate and adaptive immune microenvironment revealed potential correlates of susceptibility and resistance, including favorable and unfavorable cytokine profiles, differential composition of intratumoral myeloid cells, and baseline differences in tumor cell immunogenicity and tumor-infiltrating T-cell subsets. It is likely that a more complete understanding of the interplay between the immunologic immune microenvironment and virus infection will be necessary to fully leverage the antitumor effects of this therapeutic platform. |
| first_indexed | 2024-12-10T06:46:51Z |
| format | Article |
| id | doaj.art-bf8e7d0411ef44b882998c44c0e17aa8 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-10T06:46:51Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-bf8e7d0411ef44b882998c44c0e17aa82022-12-22T01:58:38ZengElsevierMolecular Therapy: Oncolytics2372-77052014-01-011C10.1038/mto.2014.10Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivityJennifer L Leddon0Chun-Yu Chen1Mark A Currier2Pin-Yi Wang3Francesca A Jung4Nicholas L Denton5Kevin M Cripe6Kellie B Haworth7Michael A Arnold8Amy C Gross9Timothy D Eubank10William F Goins11Joseph C Glorioso12Justus B Cohen13Paola Grandi14David A Hildeman15Timothy P Cripe16Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USADepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USADivision of Pulmonary, Allergy, Critical Care & Sleep Medicine, The Ohio State University, Columbus, Ohio, USADivision of Pulmonary, Allergy, Critical Care & Sleep Medicine, The Ohio State University, Columbus, Ohio, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USADivision of Cellular and Molecular Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USACenter for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USAMultiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic herpes simplex virus replication and cytotoxicity in vitro, with the most permissive being comparable to some human sarcoma tumor lines. The in vivo antitumor effect ranged from no or modest response to complete tumor regression and protection from tumor rechallenge. The in vitro permissiveness to viral oncolysis was not predictive of the in vivo antitumor effect, as all three tumors showed intact interferon signaling and minimal permissiveness to virus in vivo. Tumor shrinkage was T-cell mediated with a tumor-specific antigen response required for maximal antitumor activity. Further analysis of the innate and adaptive immune microenvironment revealed potential correlates of susceptibility and resistance, including favorable and unfavorable cytokine profiles, differential composition of intratumoral myeloid cells, and baseline differences in tumor cell immunogenicity and tumor-infiltrating T-cell subsets. It is likely that a more complete understanding of the interplay between the immunologic immune microenvironment and virus infection will be necessary to fully leverage the antitumor effects of this therapeutic platform.http://www.sciencedirect.com/science/article/pii/S2372770516300043 |
| spellingShingle | Jennifer L Leddon Chun-Yu Chen Mark A Currier Pin-Yi Wang Francesca A Jung Nicholas L Denton Kevin M Cripe Kellie B Haworth Michael A Arnold Amy C Gross Timothy D Eubank William F Goins Joseph C Glorioso Justus B Cohen Paola Grandi David A Hildeman Timothy P Cripe Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity Molecular Therapy: Oncolytics |
| title | Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity |
| title_full | Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity |
| title_fullStr | Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity |
| title_full_unstemmed | Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity |
| title_short | Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity |
| title_sort | oncolytic hsv virotherapy in murine sarcomas differentially triggers an antitumor t cell response in the absence of virus permissivity |
| url | http://www.sciencedirect.com/science/article/pii/S2372770516300043 |
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