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Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity
Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270140/ https://www.ncbi.nlm.nih.gov/pubmed/32493984 http://dx.doi.org/10.1038/s41598-020-65365-7 |
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author | Zador, Zsolt Landry, Alexander P. Balas, Michael Cusimano, Michael D. |
author_facet | Zador, Zsolt Landry, Alexander P. Balas, Michael Cusimano, Michael D. |
author_sort | Zador, Zsolt |
collection | PubMed |
description | Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment. |
format | Online Article Text |
id | pubmed-7270140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72701402020-06-05 Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity Zador, Zsolt Landry, Alexander P. Balas, Michael Cusimano, Michael D. Sci Rep Article Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment. Nature Publishing Group UK 2020-06-03 /pmc/articles/PMC7270140/ /pubmed/32493984 http://dx.doi.org/10.1038/s41598-020-65365-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zador, Zsolt Landry, Alexander P. Balas, Michael Cusimano, Michael D. Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title | Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title_full | Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title_fullStr | Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title_full_unstemmed | Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title_short | Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity |
title_sort | landscape of immune cell gene expression is unique in predominantly who grade 1 skull base meningiomas when compared to convexity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270140/ https://www.ncbi.nlm.nih.gov/pubmed/32493984 http://dx.doi.org/10.1038/s41598-020-65365-7 |
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