Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE165391 | GEO | 2021/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion.

Project description:Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Mechanistically, this is not elicited via genetic selection of tumor subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack. These changes launch a myeloid-affiliated transcriptional program, which leads to increased recruitment of tumor-associated macrophages. Furthermore, we identify similar epigenetic and transcriptional signatures in human mesenchymal subtype GSCs. We conclude that epigenetic immunoediting may drive an acquired immune evasion program in the most aggressive mesenchymal GBM subtype by reshaping the tumor immune microenvironment.

| S-EPMC8099351 | biostudies-literature

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [WGS]

Project description:Glioblastoma multiforme (GBM) is an aggressive brain tumour. Current immunotherapy approaches have been unsuccessful, highlighting the need to determine underlying mechanisms of immune evasion. Here, we developed syngeneic immunocompetent mouse models of GBM to explore this. GBM stem cells (GSCs) were serially transplanted through immunocompetent hosts, which uncovered an acquired capability to escape immune clearance through an enhanced immunosuppressive tumour microenvironment. Mechanistically, this was not elicited via genetic selection of tumour subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack. These include activation of interferon signalling modules, myeloid-affiliated transcription factors and chemokines, which leads to increased recruitment of tumour-associated macrophages. Furthermore, we identify similar epigenetic and transcriptional signatures in human mesenchymal subtype GSCs. We conclude that epigenetic immunoediting may drive an acquired immune evasion program in the most aggressive mesenchymal GBM subtype by reshaping the tumour immune microenvironment.

2021-04-30 | GSE165390 | GEO

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [BiSulfite-seq]

2021-04-30 | GSE165389 | GEO

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [RNA-seq]

2021-04-30 | GSE165386 | GEO

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

Project description:Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

| PRJNA694308 | ENA

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [WGS]

Project description:Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [WGS]

| PRJNA694309 | ENA

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [RNA-seq]

Project description:Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [RNA-seq]

| PRJNA694302 | ENA

Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [BiSulfite-seq]

Project description:Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [BiSulfite-seq]

| PRJNA694305 | ENA

CD8<sup>+</sup> T-cell-Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas.

Project description:PurposeCancer immunoediting shapes tumor progression by the selection of tumor cell variants that can evade immune recognition. Given the immune evasion and intratumor heterogeneity characteristic of gliomas, we hypothesized that CD8+ T cells mediate immunoediting in these tumors.Experimental designWe developed retrovirus-induced PDGF+ Pten -/- murine gliomas and evaluated glioma progression and tumor immunogenicity in the absence of CD8+ T cells by depleting this immune cell population. Furthermore, we characterized the genomic alterations present in gliomas that developed in the presence and absence of CD8+ T cells.ResultsUpon transplantation, gliomas that developed in the absence of CD8+ T cells engrafted poorly in recipients with intact immunity but engrafted well in those with CD8+ T-cell depletion. In contrast, gliomas that developed under pressure from CD8+ T cells were able to fully engraft in both CD8+ T-cell-depleted mice and immunocompetent mice. Remarkably, gliomas developed in the absence of CD8+ T cells exhibited increased aneuploidy, MAPK pathway signaling, gene fusions, and macrophage/microglial infiltration, and showed a proinflammatory phenotype. MAPK activation correlated with macrophage/microglia recruitment in this model and in the human disease.ConclusionsOur studies indicate that, in these tumor models, CD8+ T cells influence glioma oncogenic pathways, tumor genotype, and immunogenicity. This suggests immunoediting of immunogenic tumor clones through their negative selection by CD8+ T cells during glioma formation.

| S-EPMC7442699 | biostudies-literature

Invasive glioblastoma cells acquire stemness and increased Akt activation.

Project description:Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core) and invasive (Inv) cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk) down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.

| S-EPMC2887086 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data