Multiomics Analysis Reveals the Prognostic Non-tumor Cell Landscape in Glioblastoma Niches

A comprehensive characterization of non-tumor cells in the niches of primary glioblastoma is not fully established yet. This study aims to present an overview of non-malignant cells in the complex microenvironment of glioblastoma with detailed characterizations of their prognostic effects. We curate 540 gene signatures covering a total of 64 non-tumor cell types. Cell type-specific expression patterns are interrogated by normalized enrichment score across four large gene expression profiling cohorts of glioblastoma with a total number of 967 cases. The glioblastoma multiforms (GBMs) in each cohort are hierarchically clustered into negative or positive immune response classes with significantly different overall survival. Our results show that astrocytes, macrophages, monocytes, NKTs, and MSC are risk factors, while CD8 T cells, CD8 naive T cells, and plasma cells are protective factors. Moreover, we find that the immune system and organogenesis are uniformly enriched in negative immune response clusters, in contrast to the enrichment of nervous system in positive immune response clusters. Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters is independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63 to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70 to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.

• Publication year

  2021

• Venue

  Frontiers in Genetics

• Publication date

  2021-09-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fgene.2021.741325PMID 34603399PMCID 8481948
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• SciBet as a portable and fast single cell type identifier

  2020cited by this paper
• Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies

  2020cited by this paper
• neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival

  2020cited by this paper
• Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

  2019cited by this paper
• The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival

  2019cited by this paper
• Comprehensive integration of single cell data

  2018cited by this paper
• Reactive Astrocytes in Glioblastoma Multiforme

  2018cited by this paper
• Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

  2018cited by this paper
• Integrating single-cell transcriptomic data across different conditions, technologies, and species

  2018cited by this paper
• Single-cell transcriptome analysis of lineage diversity in high-grade glioma

  2018cited by this paper
• Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor.

  2018cited by this paper
• Interleukin-8/CXCR2 signaling regulates therapy-induced plasticity and enhances tumorigenicity in glioblastoma

  2018cited by this paper
• The REMBRANDT study, a large collection of genomic data from brain cancer patients

  2018cited by this paper
• Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma

  2017cited by this paper
• Myeloid-Derived Suppressor Cells

  2017cited by this paper
• Immunotherapies for Malignant Glioma

  2017cited by this paper
• Comprehensive RNA-seq transcriptomic profiling in the malignant progression of gliomas

  2017cited by this paper
• Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment.

  2017cited by this paper
• Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

  2017cited by this paper
• A metabolic function of FGFR3-TACC3 gene fusions in cancer

  2017cited by this paper
• Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer

  2017cited by this paper
• xCell: digitally portraying the tissue cellular heterogeneity landscape

  2017cited by this paper
• Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

  2016cited by this paper
• Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

  2016cited by this paper
• Clonal evolution of glioblastoma under therapy

  2016cited by this paper
• Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade

  2016cited by this paper
• CGCG clinical practice guidelines for the management of adult diffuse gliomas.

  2016cited by this paper
• Molecular and genetic properties of tumors associated with local immune cytolytic activity.

  2015cited by this paper
• The role of microglia and macrophages in glioma maintenance and progression

  2015cited by this paper
• Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups

  2015cited by this paper
• Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth

  2014cited by this paper
• The cellular and molecular origin of tumor-associated macrophages

  2014cited by this paper
• RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

  2014cited by this paper
• Activation of Glioma Cells Generates Immune Tolerant NKT Cells*

  2014cited by this paper
• The somatic genomic landscape of glioblastoma.

  2013cited by this paper
• Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells.

  2013cited by this paper
• Interleukins in glioblastoma pathophysiology: implications for therapy

  2013cited by this paper
• Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

  2013cited by this paper
• Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma.

  2013cited by this paper
• Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells

  2013cited by this paper
• Interleukin-1β and transforming growth factor-β cooperate to induce neurosphere formation and increase tumorigenicity of adherent LN-229 glioma cells

  2012cited by this paper
• Tumor-Associated Microglia/Macrophages Enhance the Invasion of Glioma Stem-like Cells via TGF-β1 Signaling Pathway

  2012cited by this paper
• Molecular signatures database (MSigDB) 3.0

  2011cited by this paper
• Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

  2011cited by this paper
• Glioma cancer stem cells induce immunosuppressive macrophages/microglia.

  2010cited by this paper
• CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival.

  2010cited by this paper
• Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.

  2010cited by this paper
• Comprehensive genomic characterization defines human glioblastoma genes and core pathways

  2008influential reference
• An Integrated Genomic Analysis of Human Glioblastoma Multiforme

  2008cited by this paper
• Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

  2006cited by this paper
• Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain

  2005cited by this paper
• MGMT gene silencing and benefit from temozolomide in glioblastoma.

  2005cited by this paper
• Immunology and Immunotherapy

  2005cited by this paper
• Epidemiology and etiology of gliomas

  2005cited by this paper
• From the Cover: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

  2005cited by this paper
• Modulation of major histocompatibility complex Class I molecules and major histocompatibility complex-bound immunogenic peptides induced by interferon-alpha and interferon-gamma treatment of human glioblastoma multiforme.

  2004cited by this paper
• Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model.

  2003cited by this paper
• Immunology and Immunotherapy in Neurosurgical Disease

  2003cited by this paper
• Cytoscape: a software environment for integrated models of biomolecular interaction networks.

  2003cited by this paper
• PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme

  2001cited by this paper
• Loss of Heterozygosity on Chromosome 19 in Secondary Glioblastomas

  2000cited by this paper
• Loss of heterozygosity on chromosome 10, 13q(Rb), 17p, and p53 gene mutations in human brain gliomas.

  1995cited by this paper
• Region‐specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma

  1995cited by this paper
• The New WHO Classification of Brain Tumours

  1993cited by this paper
• A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis

  1970cited by this paper

• No citing papers are available for this paper.