Symbiotic macrophage-glioma cell interactions in the tumor microenvironment reveal GBM therapeutic vulnerabilities
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ABSTRACT:
PROVIDER: PRJNA504456 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-08 | GSE122285 | GEO
Project description:Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult glioblastomas (GBM). Thus, we directly compared inflammatory characteristics of DIPG and adult GBM. We found that the leukocyte (CD45+) compartment in primary DIPG tissue samples is predominantly composed of CD11b+ macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant in adult GBM tissue samples. RNA sequencing of macrophages isolated from primary tumor samples revealed that DIPG- and adult GBM-associated macrophages both express gene programs related to ECM remodeling and angiogenesis, but DIPG-associated macrophages express substantially fewer inflammatory factors than their adult GBM counterparts. Examining the secretome of glioma cells, we found that patient-derived DIPG cell cultures secrete markedly fewer cytokines and chemokines than patient-derived adult GBM cultures. Concordantly, bulk and single-cell RNA sequencing data indicates low to absent expression of chemokines and cytokines in DIPG. Together, these observations suggest that the inflammatory milieu of the DIPG tumor microenvironment is fundamentally different than adult GBM. The low intrinsic inflammatory signature of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory phenotype of DIPG-associated microglia/macrophages. Understanding the glioma subtype-specific inflammatory milieu may inform the design and application of immunotherapy-based treatments.
2018-08-23 | GSE115397 | GEO
Project description:The DNA methylation profiles of Glioma Stem Cell (GSC) lines were investigated in order to find the stem cell signature associated to glioblastoma (GBM). This goal was achieved through the comparison of GSC methylation data with FFPE-GBM biopsies and human foetal Neural Stem Cell (NSC) lines profiles. GSC lines: 3 (GBM2, G144, G166). FFPE-GBM biopsy pool: FFPE-GBM pool: 1 pool from 5 GBM biopsies. Human foetal NSC lines: 2 (CB660 from forebrain; CB660SP form spinal cord). Methylated DNA from each sample was enriched with the immunoprecipitation method using 5-methylcytosine antibody (Eurogentec). Immunoprecipitated DNA (IP-DNA) and total DNA were labeled and hybridized on Agilent Human CpG Island ChIP-on-Chip Microarray 244K. IP-DNA were labeled with Cy5 while the matching total DNA were labeled with Cy3.
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Project description:In order to further understand how glioma-derived IL-33 is orchestrating changes within the tumor microenvironment and based on the significant increase of anti-inflammatory mediators including a number of signaling molecules observed in IL-33+ tumors, we performed phospho-proteomic analysis using mass spectrometry on the brains of tumor-bearing mice.
2020-08-28 | PXD021100 | Pride
Project description:The DNA methylation profiles of Glioma Stem Cell (GSC) lines were investigated in order to find the stem cell signature associated to glioblastoma (GBM). This goal was achieved through the comparison of GSC methylation data with FFPE-GBM biopsies and human foetal Neural Stem Cell (NSC) lines profiles.
2013-03-08 | GSE41824 | GEO
Project description:Glioblastoma multiforme (GBM) is a highly malignant brain cancer, and microglial cells play a critical role in its progression. Activation of microglia can either promote or inhibit GBM growth depending on the stage of tumour development and on the microenvironment. As current treatments for GBM have limited efficacy, there is an urgent need to develop novel strategies based on nanoplatforms for drug delivery and efficient targeting. This study investigated the microglial response and the therapeutic efficacy of dual cell membrane-coated and doxorubicin-loaded hexagonal boron nitride nanoplatelets, tested on human microglia and GBM cells. The results showed promising therapeutic effects on glioma cells and an M2 microglia polarization, highlighted through proteomic analysis.
2024-01-26 | PXD043557 | Pride
Project description:The recent incorporation of molecular features into the diagnosis of Glioblastoma Multiforme patients has led to an improved categorisation into different tumour subtypes with different prognosis and disease management. In this work, we have exploited the benefits of genome-wide multiomic approaches to identify potential molecular vulnerabilities existing on GBM patients. We used the Illumina MethylationEPIC Beadchip platform to describe the genome-wide 5mC and 5hmC DNA methylation landscape of a total of 9 patient-derived Glioblastoma Multiforme Cell lines obtained from the human glioblastoma cell culture resource (HGCC) and 4 brain samples obtained from non-tumoral controls
2023-06-01 | E-MTAB-12473 | biostudies-arrayexpress
Project description:Background: Signaling by receptor tyrosine kinases (RTK) is frequently dysregulated in gliomas. Inter-individual variability in the causes for dysregulated RTK signaling may have hampered the efficacy of targeted therapies. Using gene expression modules around key regulators in the RAS-RAF-MEK-MAPK cascade and in the phosphatidylinositol 3-kinase-AKT pathways, we developed a âRMPAâ clustering scheme to distinguish gliomas with varying extents of RTK signaling. Results: We identified gene modules consistently co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) in gliomas. Their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV into RMPAhigh and RMPAlow phenotypes in a morphology-independent manner. In five independent data sets from three continents containing more than 1500 adult diffuse gliomas, RMPAhigh gliomas were associated with poor prognosis while RMPAlow gliomas were not. The RMPAhigh and RMPAlow glioma subtypes showed distinct levels of the activities of RAS-RAF-MEK-MAPK cascade and PI3K-AKT pathway and harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas contained large numbers of immature vessel cells and tumor associated macrophages and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. Conclusion: Inter-glioma variability in RTK signaling activities can be defined using the RMPA clustering scheme. The combined signatures of NF1-M, SPRY-M and PTEN-M reflect RTK signaling activity both in the glioma cells and in the glioma microenvironment. Our data show that RTK signaling in the glioma microenvironment may play a pivotal role in glioma progression. Transcriptome data from 22 fresh gliomas (2 astrocytoma II, 1 oligodendrocytoma II, 7 oligoastrocytoma II, 4 anaplastic oligoastrocytoma III and 8 GBM) were obtained using Affymetrix Human Gene 1.0 ST Array. Unsupervised hierarchical clustering of the expression data for the SPRY-M, NF1-M and PTEN-M was performed on these transcriptome data to identify samples with RMPAhigh or RMPAlow signature.
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Project description:Our main objective was to study genome-wide differential methylation in de novo glioblastoma multiforme (GBM, grade IV glioma). We evaluated CpG sites in gene promoters of 26,000+ genes using an array-based chip. We retrieved 54 GBM from biorepositories of two institutions(40 from Columbia University and 14 from Case Western Reserve University) and 24 control brain tissues from the New York Brain Bank, which collected control brain tissues from consented subjects without history of neurological diseases at autopsy. Bisulfite modified DNA was extracted from 54 GBM and 24 control brain tissue. The HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in the autosomes.
2013-10-18 | E-GEOD-50923 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. The hypoxic tumor microenvironment has been shown to play an important role to maintain the GICs; however, the mechanisms regulating responses of GICs to hypoxia remain poorly understood.
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