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.
Recommended Citation
Wang, Qianghu; Hu, Baoli; Hu, Xin; Kim, Hoon; Squatrito, Massimo; Scarpace, Lisa; deCarvalho, Ana C; Lyu, Sali; Li, Pengping; Li, Yan; Barthel, Floris P; Cho, Hee Jin; Lin, Yu-Hsi; Satani, Nikunj; Martinez-Ledesma, Emmanuel; Zheng, Siyuan; Chang, Edward; Sauvé, Charles-Etienne Gabriel; Olar, Adriana; Lan, Zheng D; Finocchiaro, Gaetano; Phillips, Joanna J; Berger, Mitchel S; Gabrusiewicz, Konrad R; Wang, Guocan; Eskilsson, Eskil; Hu, Jian; Mikkelsen, Tom; DePinho, Ronald A; Muller, Florian; Heimberger, Amy B; Sulman, Erik P; Nam, Do-Hyun; and Verhaak, Roel G W, "Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment." (2017). Faculty Research 2017. 142.
https://mouseion.jax.org/stfb2017/142