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Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma

SIMPLE SUMMARY: Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with dismal survival and poor response to conventional therapies. Therefore, the development of immunotherapy for GBM treatment is necessary. However, the rigorous immunosuppression in the GBM-microenvironment (...

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Autores principales: Jin, Ketao, Mao, Chunsen, Chen, Lin, Wang, Lude, Liu, Yuyao, Yuan, Jianlie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826839/
https://www.ncbi.nlm.nih.gov/pubmed/33435205
http://dx.doi.org/10.3390/cancers13020229
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author Jin, Ketao
Mao, Chunsen
Chen, Lin
Wang, Lude
Liu, Yuyao
Yuan, Jianlie
author_facet Jin, Ketao
Mao, Chunsen
Chen, Lin
Wang, Lude
Liu, Yuyao
Yuan, Jianlie
author_sort Jin, Ketao
collection PubMed
description SIMPLE SUMMARY: Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with dismal survival and poor response to conventional therapies. Therefore, the development of immunotherapy for GBM treatment is necessary. However, the rigorous immunosuppression in the GBM-microenvironment (GME) is a crucial impediment for GBM immunotherapy. The adenosinergic pathway (AP) is a major player in suppressing antitumor immune responses in the GME. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. Tumor cells metabolize pro-inflammatory ATP to anti-inflammatory adenosine using CD39 and CD73 enzymes. Adenosine suppresses immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in the GBM showed promising results in reinvigorating antitumor responses and overriding chemoresistance. We suggest that future clinical studies should consider this pathway in combination therapies along with other immunotherapeutic approaches. ABSTRACT: Brain tumors comprise different types of malignancies, most of which are originated from glial cells. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with a poor response to conventional therapies and dismal survival rates (15 months) despite multimodal therapies. The development of immunotherapeutic strategies seems to be necessary to enhance the overall survival of GBM patients. So far, the immunotherapies applied in GBM had promising results in the primary phases of clinical trials but failed to continue their beneficial effects in later phases. GBM-microenvironment (GME) is a heterogenic and rigorously immunosuppressive milieu wrapping by an impenetrable blood-brain barrier. Hence, in-depth knowledge about the dominant immunosuppressive mechanisms in the GME could foster GBM immunotherapy. Recently, the adenosinergic pathway (AP) is found to be a major player in the suppression of antitumor immune responses in the GME. Tumor cells evolve to metabolize pro-inflammatory ATP to anti-inflammatory adenosine. Adenosine can suppress immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in GBM showed promising results in reinvigorating antitumor responses, overriding chemoresistance, and increasing survival. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. We suggest that future clinical studies should consider this pathway in their combination therapies along with other immunotherapeutic approaches.
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spelling pubmed-78268392021-01-25 Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma Jin, Ketao Mao, Chunsen Chen, Lin Wang, Lude Liu, Yuyao Yuan, Jianlie Cancers (Basel) Review SIMPLE SUMMARY: Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with dismal survival and poor response to conventional therapies. Therefore, the development of immunotherapy for GBM treatment is necessary. However, the rigorous immunosuppression in the GBM-microenvironment (GME) is a crucial impediment for GBM immunotherapy. The adenosinergic pathway (AP) is a major player in suppressing antitumor immune responses in the GME. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. Tumor cells metabolize pro-inflammatory ATP to anti-inflammatory adenosine using CD39 and CD73 enzymes. Adenosine suppresses immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in the GBM showed promising results in reinvigorating antitumor responses and overriding chemoresistance. We suggest that future clinical studies should consider this pathway in combination therapies along with other immunotherapeutic approaches. ABSTRACT: Brain tumors comprise different types of malignancies, most of which are originated from glial cells. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with a poor response to conventional therapies and dismal survival rates (15 months) despite multimodal therapies. The development of immunotherapeutic strategies seems to be necessary to enhance the overall survival of GBM patients. So far, the immunotherapies applied in GBM had promising results in the primary phases of clinical trials but failed to continue their beneficial effects in later phases. GBM-microenvironment (GME) is a heterogenic and rigorously immunosuppressive milieu wrapping by an impenetrable blood-brain barrier. Hence, in-depth knowledge about the dominant immunosuppressive mechanisms in the GME could foster GBM immunotherapy. Recently, the adenosinergic pathway (AP) is found to be a major player in the suppression of antitumor immune responses in the GME. Tumor cells evolve to metabolize pro-inflammatory ATP to anti-inflammatory adenosine. Adenosine can suppress immune responses through the signaling of adenosine receptors on immune cells. The preclinical results targeting AP in GBM showed promising results in reinvigorating antitumor responses, overriding chemoresistance, and increasing survival. We reviewed the current GBM immunotherapies and elaborated on the role of AP in the immunopathogenesis, treatment, and even prognosis of GBM. We suggest that future clinical studies should consider this pathway in their combination therapies along with other immunotherapeutic approaches. MDPI 2021-01-10 /pmc/articles/PMC7826839/ /pubmed/33435205 http://dx.doi.org/10.3390/cancers13020229 Text en © 2021 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
Jin, Ketao
Mao, Chunsen
Chen, Lin
Wang, Lude
Liu, Yuyao
Yuan, Jianlie
Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title_full Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title_fullStr Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title_full_unstemmed Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title_short Adenosinergic Pathway: A Hope in the Immunotherapy of Glioblastoma
title_sort adenosinergic pathway: a hope in the immunotherapy of glioblastoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826839/
https://www.ncbi.nlm.nih.gov/pubmed/33435205
http://dx.doi.org/10.3390/cancers13020229
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