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PD-L1/PD-1 Axis in Glioblastoma Multiforme
Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates arou...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862444/ https://www.ncbi.nlm.nih.gov/pubmed/31661771 http://dx.doi.org/10.3390/ijms20215347 |
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author | Litak, Jakub Mazurek, Marek Grochowski, Cezary Kamieniak, Piotr Roliński, Jacek |
author_facet | Litak, Jakub Mazurek, Marek Grochowski, Cezary Kamieniak, Piotr Roliński, Jacek |
author_sort | Litak, Jakub |
collection | PubMed |
description | Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme. |
format | Online Article Text |
id | pubmed-6862444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68624442019-12-05 PD-L1/PD-1 Axis in Glioblastoma Multiforme Litak, Jakub Mazurek, Marek Grochowski, Cezary Kamieniak, Piotr Roliński, Jacek Int J Mol Sci Review Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme. MDPI 2019-10-28 /pmc/articles/PMC6862444/ /pubmed/31661771 http://dx.doi.org/10.3390/ijms20215347 Text en © 2019 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 Litak, Jakub Mazurek, Marek Grochowski, Cezary Kamieniak, Piotr Roliński, Jacek PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title | PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title_full | PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title_fullStr | PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title_full_unstemmed | PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title_short | PD-L1/PD-1 Axis in Glioblastoma Multiforme |
title_sort | pd-l1/pd-1 axis in glioblastoma multiforme |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862444/ https://www.ncbi.nlm.nih.gov/pubmed/31661771 http://dx.doi.org/10.3390/ijms20215347 |
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