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Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma

There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing signifi...

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Autores principales: Du, Ziming, Abedalthagafi, Malak, Aizer, Ayal A., McHenry, Allison R., Sun, Heather H., Bray, Mark-Anthony, Viramontes, Omar, Machaidze, Revaz, Brastianos, Priscilla K., Reardon, David A., Dunn, Ian F., Freeman, Gordon J., Ligon, Keith L., Carpenter, Anne E., Alexander, Brian M., Agar, Nathalie Y., Rodig, Scott J., Bradshaw, Elizabeth M., Santagata, Sandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467109/
https://www.ncbi.nlm.nih.gov/pubmed/25609200
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author Du, Ziming
Abedalthagafi, Malak
Aizer, Ayal A.
McHenry, Allison R.
Sun, Heather H.
Bray, Mark-Anthony
Viramontes, Omar
Machaidze, Revaz
Brastianos, Priscilla K.
Reardon, David A.
Dunn, Ian F.
Freeman, Gordon J.
Ligon, Keith L.
Carpenter, Anne E.
Alexander, Brian M.
Agar, Nathalie Y.
Rodig, Scott J.
Bradshaw, Elizabeth M.
Santagata, Sandro
author_facet Du, Ziming
Abedalthagafi, Malak
Aizer, Ayal A.
McHenry, Allison R.
Sun, Heather H.
Bray, Mark-Anthony
Viramontes, Omar
Machaidze, Revaz
Brastianos, Priscilla K.
Reardon, David A.
Dunn, Ian F.
Freeman, Gordon J.
Ligon, Keith L.
Carpenter, Anne E.
Alexander, Brian M.
Agar, Nathalie Y.
Rodig, Scott J.
Bradshaw, Elizabeth M.
Santagata, Sandro
author_sort Du, Ziming
collection PubMed
description There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma – both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.
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spelling pubmed-44671092015-06-22 Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma Du, Ziming Abedalthagafi, Malak Aizer, Ayal A. McHenry, Allison R. Sun, Heather H. Bray, Mark-Anthony Viramontes, Omar Machaidze, Revaz Brastianos, Priscilla K. Reardon, David A. Dunn, Ian F. Freeman, Gordon J. Ligon, Keith L. Carpenter, Anne E. Alexander, Brian M. Agar, Nathalie Y. Rodig, Scott J. Bradshaw, Elizabeth M. Santagata, Sandro Oncotarget Research Paper There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma – both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors. Impact Journals LLC 2014-12-31 /pmc/articles/PMC4467109/ /pubmed/25609200 Text en Copyright: © 2015 Du et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Du, Ziming
Abedalthagafi, Malak
Aizer, Ayal A.
McHenry, Allison R.
Sun, Heather H.
Bray, Mark-Anthony
Viramontes, Omar
Machaidze, Revaz
Brastianos, Priscilla K.
Reardon, David A.
Dunn, Ian F.
Freeman, Gordon J.
Ligon, Keith L.
Carpenter, Anne E.
Alexander, Brian M.
Agar, Nathalie Y.
Rodig, Scott J.
Bradshaw, Elizabeth M.
Santagata, Sandro
Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title_full Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title_fullStr Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title_full_unstemmed Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title_short Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma
title_sort increased expression of the immune modulatory molecule pd-l1 (cd274) in anaplastic meningioma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467109/
https://www.ncbi.nlm.nih.gov/pubmed/25609200
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