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.
Recommended Citation
Wang Q,
Hu B,
Hu X,
Kim H,
Squatrito M,
Scarpace L,
deCarvalho A,
Lyu S,
Li P,
Li Y,
Barthel F,
Cho H,
Lin Y,
Satani N,
Martinez-Ledesma E,
Zheng S,
Chang E,
Sauvé C,
Olar A,
Lan Z,
Finocchiaro G,
Phillips J,
Berger M,
Gabrusiewicz K,
Wang G,
Eskilsson E,
Hu J,
Mikkelsen T,
DePinho R,
Muller F,
Heimberger A,
Sulman E,
Nam D,
Verhaak R.
Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell 2017 Jul 10; 32(1):42-56.e6