Cargando…

Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas

PURPOSE: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogeni...

Descripción completa

Detalles Bibliográficos
Autores principales: Nesseler, Jean Philippe, Schaue, Dorthe, McBride, William H., Lee, Mi-Heon, Kaprealian, Tania, Niclou, Simone P., Nickers, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460102/
https://www.ncbi.nlm.nih.gov/pubmed/31011672
http://dx.doi.org/10.1016/j.adro.2018.11.005
_version_ 1783410282351034368
author Nesseler, Jean Philippe
Schaue, Dorthe
McBride, William H.
Lee, Mi-Heon
Kaprealian, Tania
Niclou, Simone P.
Nickers, Philippe
author_facet Nesseler, Jean Philippe
Schaue, Dorthe
McBride, William H.
Lee, Mi-Heon
Kaprealian, Tania
Niclou, Simone P.
Nickers, Philippe
author_sort Nesseler, Jean Philippe
collection PubMed
description PURPOSE: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies. METHODS AND MATERIALS: A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration. RESULTS: Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials. CONCLUSIONS: This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response.
format Online
Article
Text
id pubmed-6460102
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-64601022019-04-22 Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas Nesseler, Jean Philippe Schaue, Dorthe McBride, William H. Lee, Mi-Heon Kaprealian, Tania Niclou, Simone P. Nickers, Philippe Adv Radiat Oncol Central Nervous System PURPOSE: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies. METHODS AND MATERIALS: A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration. RESULTS: Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials. CONCLUSIONS: This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response. Elsevier 2018-11-20 /pmc/articles/PMC6460102/ /pubmed/31011672 http://dx.doi.org/10.1016/j.adro.2018.11.005 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Central Nervous System
Nesseler, Jean Philippe
Schaue, Dorthe
McBride, William H.
Lee, Mi-Heon
Kaprealian, Tania
Niclou, Simone P.
Nickers, Philippe
Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title_full Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title_fullStr Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title_full_unstemmed Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title_short Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
title_sort irradiation to improve the response to immunotherapeutic agents in glioblastomas
topic Central Nervous System
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460102/
https://www.ncbi.nlm.nih.gov/pubmed/31011672
http://dx.doi.org/10.1016/j.adro.2018.11.005
work_keys_str_mv AT nesselerjeanphilippe irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT schauedorthe irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT mcbridewilliamh irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT leemiheon irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT kaprealiantania irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT niclousimonep irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas
AT nickersphilippe irradiationtoimprovetheresponsetoimmunotherapeuticagentsinglioblastomas