Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells Journal Article

   

Authors:	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.
Article Title:	Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells
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. © 2020 Elsevier Inc. High-dimensional, multi-omics characterization of the brain tumor microenvironment, including comparisons of gliomas and brain metastases, suggests that education of immune cell types in the TME depends on tumor origin and IDH mutational status. © 2020 Elsevier Inc.
Keywords:	glioma; t cells; glioblastoma; brain metastasis; neutrophils; tumor microenvironment; microglia; cancer immunology; monocyte-derived macrophages; tumor-associated macrophages
Journal Title:	Cell
Volume:	181
Issue:	7
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2020-06-25
Start Page:	1643
End Page:	1660.e17
Language:	English
DOI:	10.1016/j.cell.2020.05.007
PUBMED:	32470396
PROVIDER:	scopus
PMCID:	PMC8558904
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086386623&doi=10.1016%2fj.cell.2020.05.007&partnerID=40&md5=01f453e51a18f9e685652970afb5d0fd
Notes:	Article -- Export Date: 3 August 2020 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/168661