Title

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment.

Document Type

Article

Publication Date

7-10-2017

JAX Source

Cancer Cell 2017 Jul 10; 32(1):42-56.e6

Volume

32

Issue

1

First Page

42

Last Page

56

ISSN

1878-3686

PMID

28697342

DOI

https://doi.org/10.1016/j.ccell.2017.06.003

Grant

CA127001, CA190121, CA034196

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. Cancer Cell 2017 Jul 10; 32(1):42-56.e6.

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