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Wang, Qianghu; Hu, Baoli; Hu, Xin; Kim, Hoon; Squatrito, Massimo; Scarpace, Lisa; deCarvalho, Ana C.; Lyu, Sali; Li, Pengping; Li, Yan; Barthel, Floris; 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; Verhaak, Roel G.W.
Cancer cell, 07/2017, Letnik: 32, Številka: 1Journal Article
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. Display omitted •GBM-intrinsic transcriptional subtypes: proneural, classical, mesenchymal•NF1 deficiency drives recruitment of tumor-associated macrophages/microglia•Resistance to radiotherapy may associate with M2 macrophage presence•CD8+ T cells are enriched in temozolomide-induced hypermutated GBMs at recurrence 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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