Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment
- PMID: 28697342
- PMCID: PMC5599156
- DOI: 10.1016/j.ccell.2017.06.003
Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment
Erratum in
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Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment.Cancer Cell. 2018 Jan 8;33(1):152. doi: 10.1016/j.ccell.2017.12.012. Cancer Cell. 2018. PMID: 29316430 Free PMC article. No abstract available.
Abstract
We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.
Keywords: disease recurrence; glioblastoma; immune cells; macrophages/microglia; mesenchymal subtype; proneural to mesenchymal transition; tumor evolution; tumor microenvironment.
Copyright © 2017 Elsevier Inc. All rights reserved.
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References
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