[PDF][PDF] Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment

Q Wang, B Hu, X Hu, H Kim, M Squatrito, L Scarpace… - Cancer cell, 2017 - cell.com
Q Wang, B Hu, X Hu, H Kim, M Squatrito, L Scarpace, AC DeCarvalho, S Lyu, P Li, Y Li…
Cancer cell, 2017cell.com
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 …
Summary
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.
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