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EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS
BACKGROUND: Ependymomas account for 8–10% of pediatric brain tumors, and the standard therapy of surgery and radiation has not changed for the past two decades. Characterization of the tumor immune microenvironment (TIME) is of great importance in order to find better therapies. However, the TIME of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168173/ http://dx.doi.org/10.1093/neuonc/noab090.060 |
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author | F. Feenstra, Fenna Calkoen, Friso Kros, Johan M Kester, Lennart Kranendonk, Mariëtte van der Lugt, Jasper Mustafa, Dana A M |
author_facet | F. Feenstra, Fenna Calkoen, Friso Kros, Johan M Kester, Lennart Kranendonk, Mariëtte van der Lugt, Jasper Mustafa, Dana A M |
author_sort | F. Feenstra, Fenna |
collection | PubMed |
description | BACKGROUND: Ependymomas account for 8–10% of pediatric brain tumors, and the standard therapy of surgery and radiation has not changed for the past two decades. Characterization of the tumor immune microenvironment (TIME) is of great importance in order to find better therapies. However, the TIME of ependymomas is still not defined. In this retrospective observational study we aimed to unravel the TIME of ependymomas at mRNA and protein expression levels. METHODS: Ependymoma samples from two locations were selected: Posterior Fossa (PF-A, n=8), and supratentorial (ST, n=5). Targeted gene expression profile using the PanCancer immune profile panel of NanoString technology was performed. Data were analyzed using the nSolver software. In addition, 8 samples were subjected to RNA bulk sequencing, and the sequenced data were connected to the expression data of the same samples. To validate some of the findings, immunohistochemistry was performed. RESULTS: Unsupervised hierarchical clustering showed that PF-A ependymomas can be divided into two groups based on the expression of their immune-related genes. PF-A that showed high immune-expression clustered closely to the ST ependymomas. Significant expressions of genes related to “antigen-processing” and “adhesion” pathways were found in the immune-active groups. On the contrary, the PF-A that had low expressions of immune-related genes showed a high expression of BMI1 that has a prognostic and therapeutic value. Connecting gene expression to bulk sequence data validated the findings. In addition, immunohistochemical analysis confirmed that protein expression for some of the findings. CONCLUSION: The TIME varies in ependymomas based on the location of the tumor. Moreover, the immune-related expression profiles indicated that PF-A ependymomas can be divided into two groups: immune-active and immune-not active PF-A. The prognostic and therapeutic values of the immune activity of PF-A should be further studied. |
format | Online Article Text |
id | pubmed-8168173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81681732021-06-02 EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS F. Feenstra, Fenna Calkoen, Friso Kros, Johan M Kester, Lennart Kranendonk, Mariëtte van der Lugt, Jasper Mustafa, Dana A M Neuro Oncol Ependymoma BACKGROUND: Ependymomas account for 8–10% of pediatric brain tumors, and the standard therapy of surgery and radiation has not changed for the past two decades. Characterization of the tumor immune microenvironment (TIME) is of great importance in order to find better therapies. However, the TIME of ependymomas is still not defined. In this retrospective observational study we aimed to unravel the TIME of ependymomas at mRNA and protein expression levels. METHODS: Ependymoma samples from two locations were selected: Posterior Fossa (PF-A, n=8), and supratentorial (ST, n=5). Targeted gene expression profile using the PanCancer immune profile panel of NanoString technology was performed. Data were analyzed using the nSolver software. In addition, 8 samples were subjected to RNA bulk sequencing, and the sequenced data were connected to the expression data of the same samples. To validate some of the findings, immunohistochemistry was performed. RESULTS: Unsupervised hierarchical clustering showed that PF-A ependymomas can be divided into two groups based on the expression of their immune-related genes. PF-A that showed high immune-expression clustered closely to the ST ependymomas. Significant expressions of genes related to “antigen-processing” and “adhesion” pathways were found in the immune-active groups. On the contrary, the PF-A that had low expressions of immune-related genes showed a high expression of BMI1 that has a prognostic and therapeutic value. Connecting gene expression to bulk sequence data validated the findings. In addition, immunohistochemical analysis confirmed that protein expression for some of the findings. CONCLUSION: The TIME varies in ependymomas based on the location of the tumor. Moreover, the immune-related expression profiles indicated that PF-A ependymomas can be divided into two groups: immune-active and immune-not active PF-A. The prognostic and therapeutic values of the immune activity of PF-A should be further studied. Oxford University Press 2021-06-01 /pmc/articles/PMC8168173/ http://dx.doi.org/10.1093/neuonc/noab090.060 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Ependymoma F. Feenstra, Fenna Calkoen, Friso Kros, Johan M Kester, Lennart Kranendonk, Mariëtte van der Lugt, Jasper Mustafa, Dana A M EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title | EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title_full | EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title_fullStr | EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title_full_unstemmed | EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title_short | EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS |
title_sort | epen-10. unravelling the tumor immune microenvironment of posterior fossa a ependymomas on rna and protein expression levels |
topic | Ependymoma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168173/ http://dx.doi.org/10.1093/neuonc/noab090.060 |
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