@article{6c102f9d33904aa6a0e307e0c340a863,
title = "Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment",
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. Wang et al. define three IDH wild-type glioblastoma-intrinsic gene expression subtypes, which are partly shaped by the tumor immune environment. NF1 deficiency results in increased macrophage/microglia infiltration. Comparison of matched primary and recurrent tumors reveals frequent expression subtype changes.",
keywords = "disease recurrence, glioblastoma, immune cells, macrophages/microglia, mesenchymal subtype, proneural to mesenchymal transition, tumor evolution, tumor microenvironment",
author = "Qianghu Wang and Baoli Hu and Xin Hu and Hoon Kim and Massimo Squatrito and Lisa Scarpace and deCarvalho, {Ana C.} and Sali Lyu and Pengping Li and Yan Li and Floris Barthel and Cho, {Hee Jin} and Lin, {Yu Hsi} and Nikunj Satani and Emmanuel Martinez-Ledesma and Siyuan Zheng and Edward Chang and Sauv{\'e}, {Charles Etienne Gabriel} and Adriana Olar and Lan, {Zheng D.} and Gaetano Finocchiaro and Phillips, {Joanna J.} and Berger, {Mitchel S.} and Gabrusiewicz, {Konrad R.} and Guocan Wang and Eskil Eskilsson and Jian Hu and Tom Mikkelsen and DePinho, {Ronald A.} and Florian Muller and Heimberger, {Amy B.} and Sulman, {Erik P.} and Nam, {Do Hyun} and Verhaak, {Roel G.W.}",
note = "Funding Information: The authors thank Katherine Stemke-Hale for assistance in manuscript editing. The results published here are in part based upon data generated by The Cancer Genome Atlas project established by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) of the NIH. Information about TCGA and the investigators and institutions that constitute the TCGA research network can be found at http://cancergenome.nih.gov . This work is supported by grants from the NIH , P50 CA127001 (E.P.S., F.L.M., R.G.W.V.), R01 CA190121 (E.P.S., R.G.W.V.), P50 CA097257 (M.S.B., J.J.P.), and RO1 CA120813 (A.B.H.); Cancer Center Support grants P30CA16672 and P30CA034196 ; Cancer Prevention & Research Institute of Texas (CPRIT) grant number R140606 ; the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center (R.G.W.V.); the National Brain Tumor Society Defeat GBM project (E.P.S., R.G.W.V.); the National Brain Tumor Society Oligo Research Fund (R.G.W.V.); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare , Republic of Korea ( HI14C3418 , D.H.N.); the Seve Ballesteros Foundation supported M.S.; and CPRIT RP140612 and American Cancer Society Research Scholar Grant RSG1514501CDD (F.L.M.). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jul,
day = "10",
doi = "10.1016/j.ccell.2017.06.003",
language = "English (US)",
volume = "32",
pages = "42--56.e6",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}