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The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous sys...

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Autores principales: Desland, Fiona A., Hormigo, Adília
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582539/
https://www.ncbi.nlm.nih.gov/pubmed/33027976
http://dx.doi.org/10.3390/ijms21197358
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author Desland, Fiona A.
Hormigo, Adília
author_facet Desland, Fiona A.
Hormigo, Adília
author_sort Desland, Fiona A.
collection PubMed
description Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.
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spelling pubmed-75825392020-10-29 The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy Desland, Fiona A. Hormigo, Adília Int J Mol Sci Review Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment. MDPI 2020-10-05 /pmc/articles/PMC7582539/ /pubmed/33027976 http://dx.doi.org/10.3390/ijms21197358 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Desland, Fiona A.
Hormigo, Adília
The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title_full The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title_fullStr The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title_full_unstemmed The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title_short The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy
title_sort cns and the brain tumor microenvironment: implications for glioblastoma immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582539/
https://www.ncbi.nlm.nih.gov/pubmed/33027976
http://dx.doi.org/10.3390/ijms21197358
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