Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Malo, Courtney S., Khadka, Roman H., Ayasoufi, Katayoun, Jin, Fang, AbouChehade, Jackson E., Hansen, Michael J., Iezzi, Raymond, Pavelko, Kevin D., Johnson, Aaron J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
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
_version_ 1783353059005431808
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
work_keys_str_mv AT malocourtneys immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT khadkaromanh immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT ayasoufikatayoun immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT jinfang immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT abouchehadejacksone immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT hansenmichaelj immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT iezziraymond immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT pavelkokevind immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma
AT johnsonaaronj immunomodulationmediatedbyantiangiogenictherapyimprovescd8tcellimmunityagainstexperimentalglioma