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Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma

BACKGROUND: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential...

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Autores principales: Han, Ming-Zhi, Wang, Shuai, Zhao, Wen-Bo, Ni, Shi-Lei, Yang, Ning, Kong, Yang, Huang, Bin, Chen, An-Jing, Li, Xin-Gang, Wang, Jian, Wang, Dong-Hai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557785/
https://www.ncbi.nlm.nih.gov/pubmed/30987862
http://dx.doi.org/10.1016/j.ebiom.2019.04.002
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author Han, Ming-Zhi
Wang, Shuai
Zhao, Wen-Bo
Ni, Shi-Lei
Yang, Ning
Kong, Yang
Huang, Bin
Chen, An-Jing
Li, Xin-Gang
Wang, Jian
Wang, Dong-Hai
author_facet Han, Ming-Zhi
Wang, Shuai
Zhao, Wen-Bo
Ni, Shi-Lei
Yang, Ning
Kong, Yang
Huang, Bin
Chen, An-Jing
Li, Xin-Gang
Wang, Jian
Wang, Dong-Hai
author_sort Han, Ming-Zhi
collection PubMed
description BACKGROUND: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment. METHODS: Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language. FINDINGS: HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEM(high) tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEM(low) tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment. INTERPRETATION: Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM.
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spelling pubmed-65577852019-06-13 Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma Han, Ming-Zhi Wang, Shuai Zhao, Wen-Bo Ni, Shi-Lei Yang, Ning Kong, Yang Huang, Bin Chen, An-Jing Li, Xin-Gang Wang, Jian Wang, Dong-Hai EBioMedicine Research paper BACKGROUND: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment. METHODS: Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language. FINDINGS: HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEM(high) tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEM(low) tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment. INTERPRETATION: Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM. Elsevier 2019-04-12 /pmc/articles/PMC6557785/ /pubmed/30987862 http://dx.doi.org/10.1016/j.ebiom.2019.04.002 Text en © 2019 The Authors. Published by Elsevier B.V. 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 Research paper
Han, Ming-Zhi
Wang, Shuai
Zhao, Wen-Bo
Ni, Shi-Lei
Yang, Ning
Kong, Yang
Huang, Bin
Chen, An-Jing
Li, Xin-Gang
Wang, Jian
Wang, Dong-Hai
Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title_full Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title_fullStr Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title_full_unstemmed Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title_short Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
title_sort immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557785/
https://www.ncbi.nlm.nih.gov/pubmed/30987862
http://dx.doi.org/10.1016/j.ebiom.2019.04.002
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