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Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma
Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in partic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124655/ https://www.ncbi.nlm.nih.gov/pubmed/30211113 http://dx.doi.org/10.3389/fonc.2018.00320 |
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author | Malo, Courtney S. Khadka, Roman H. Ayasoufi, Katayoun Jin, Fang AbouChehade, Jackson E. Hansen, Michael J. Iezzi, Raymond Pavelko, Kevin D. Johnson, Aaron J. |
author_facet | Malo, Courtney S. Khadka, Roman H. Ayasoufi, Katayoun Jin, Fang AbouChehade, Jackson E. Hansen, Michael J. Iezzi, Raymond Pavelko, Kevin D. Johnson, Aaron J. |
author_sort | Malo, Courtney S. |
collection | PubMed |
description | Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM. |
format | Online Article Text |
id | pubmed-6124655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61246552018-09-12 Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma Malo, Courtney S. Khadka, Roman H. Ayasoufi, Katayoun Jin, Fang AbouChehade, Jackson E. Hansen, Michael J. Iezzi, Raymond Pavelko, Kevin D. Johnson, Aaron J. Front Oncol Oncology Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM. Frontiers Media S.A. 2018-08-20 /pmc/articles/PMC6124655/ /pubmed/30211113 http://dx.doi.org/10.3389/fonc.2018.00320 Text en Copyright © 2018 Malo, Khadka, Ayasoufi, Jin, AbouChehade, Hansen, Iezzi, Pavelko and Johnson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Malo, Courtney S. Khadka, Roman H. Ayasoufi, Katayoun Jin, Fang AbouChehade, Jackson E. Hansen, Michael J. Iezzi, Raymond Pavelko, Kevin D. Johnson, Aaron J. Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title | Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title_full | Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title_fullStr | Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title_full_unstemmed | Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title_short | Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma |
title_sort | immunomodulation mediated by anti-angiogenic therapy improves cd8 t cell immunity against experimental glioma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124655/ https://www.ncbi.nlm.nih.gov/pubmed/30211113 http://dx.doi.org/10.3389/fonc.2018.00320 |
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