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 [BiSulfite-seq]

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

| PRJNA694305 | 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

Immunoediting instructs tumor metabolic reprogramming to support immune evasion.

Project description:Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by non-canonical interferon gamma (IFNγ)-STAT3 signaling and supports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells to empower them to disarm the T cell-mediated immunosurveillance by imposing metabolic tug-of-war between tumor and infiltrating T cells and forming the suppressive tumor microenvironment.

| S-EPMC10375941 | biostudies-literature

macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma.

Project description:Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2. With omics and functional assays deploying patient-derived in vitro and in vivo models, we show that macroH2A2 shapes chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. macroH2A2 also sensitizes cells to small molecule-mediated cell death via activation of a viral mimicry response. Consistent with these results, our analyses of clinical cohorts indicate that high transcriptional levels of this histone variant are associated with better prognosis of high-grade glioma patients. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest additional treatment approaches for glioblastoma patients.

| S-EPMC10224928 | biostudies-literature

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