Joshua D. Bernstock, Nunzio Vicario, Li Rong, Pablo A. Valdes, Bryan D. Choi, Jason A. Chen, Daniel DiToro, Diana S. Osorio, Kara Kachurak, Florian Geßler, James M. Johnston, T. Prescott Atkinson, Richard J. Whitley, Asim K. Bag, G. Yancey Gillespie, James M. Markert, Dragan Maric, Gregory K. Friedman
- Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient. Using this approach, we identified robust infiltration of CD8+ T cells suggesting activation of the immune response following virotherapy; however there was a corresponding upregulation of checkpoint proteins PD-1, PD-L1, CTLA-4, and IDO revealing a potential role for checkpoint inhibitors. Such work may ultimately lead to an understanding of the governing pathobiology of tumors, thereby fostering development of novel therapeutics tailored to produce optimal responses.
MetadatenAuthor: | Joshua D. BernstockORCiD, Nunzio Vicario, Li Rong, Pablo A. Valdes, Bryan D. Choi, Jason A. Chen, Daniel DiToro, Diana S. Osorio, Kara Kachurak, Florian GeßlerORCiDGND, James M. Johnston, T. Prescott Atkinson, Richard J. Whitley, Asim K. Bag, G. Yancey Gillespie, James M. Markert, Dragan Maric, Gregory K. Friedman |
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URN: | urn:nbn:de:hebis:30:3-534210 |
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DOI: | https://doi.org/10.1080/2162402X.2019.1678921 |
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ISSN: | 2162-402X |
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ISSN: | 2162-4011 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31741780 |
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Parent Title (English): | OncoImmunology |
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Publisher: | Taylor & Franics |
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Place of publication: | Abingdon |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2019 |
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Date of first Publication: | 2019/10/21 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2020/04/29 |
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Tag: | HSV; checkpoint proteins; glioma; multiplex immunofluorescence; oncolytic virotherapy |
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Volume: | 8 |
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Issue: | 12, e1678921 |
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Page Number: | 14 |
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First Page: | 1 |
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Last Page: | 14 |
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Note: | This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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HeBIS-PPN: | 465569935 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |
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