Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_B25384BE18E8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells
Journal
Cell
Author(s)
Klemm F., Maas R.R., Bowman R.L., Kornete M., Soukup K., Nassiri S., Brouland J.P., Iacobuzio-Donahue C.A., Brennan C., Tabar V., Gutin P.H., Daniel R.T., Hegi M.E., Joyce J.A.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
25/06/2020
Peer-reviewed
Oui
Volume
181
Number
7
Pages
1643-1660.e17
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells. These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-type-specific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer.
Keywords
T cells, brain metastasis, cancer immunology, glioblastoma, glioma, microglia, monocyte-derived macrophages, neutrophils, tumor microenvironment, tumor-associated macrophages
Pubmed
Web of science
Open Access
Yes
Create date
02/06/2020 15:23
Last modification date
21/04/2021 6:34
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