Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer [RNA-Seq]

ABSTRACT: Loss of MHC class I (MHC-I) antigen presentation in cancer cells can lead to immunotherapy resistance. Using a genome-wide CRISPR/Cas9 screen we identify a critical role for polycomb repressive complex 2 (PRC2) in the coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP). This evolutionarily conserved function of PRC2 promotes evasion of T-cell mediated immunity, enabling tumour transmission to non-histocompatible recipients in small cell lung cancer (SCLC) and Tasmanian Devil Facial Tumour. MHC-I APP gene promoters in MHC-I low cancers harbour bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine induced MHC-I APP gene upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological silencing of MHC-I expression highlights a conserved mechanism by which cancers arising from these primitive tissues coopt PRC2 activity to enable immune evasion.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE129381 | GEO | 2019/09/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer [ChIP-Seq]

Project description:Loss of MHC class I (MHC-I) antigen presentation in cancer cells can lead to immunotherapy resistance. Using a genome-wide CRISPR/Cas9 screen we identify a critical role for polycomb repressive complex 2 (PRC2) in the coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP). This evolutionarily conserved function of PRC2 promotes evasion of T-cell mediated immunity, enabling tumor transmission to non-histocompatible recipients in small cell lung cancer (SCLC) and Tasmanian Devil Facial Tumor. MHC-I APP gene promoters in MHC-I low cancers harbour bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine induced MHC-I APP gene upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological silencing of MHC-I expression highlights a conserved mechanism by which cancers arising from these primitive tissues coopt PRC2 activity to enable immune evasion.

2019-09-28 | GSE129380 | GEO

Project description:Tasmanian devil MHC typing

| PRJNA715496 | ENA

Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes

Project description:Transmissible cancers are spread via the passage of malignant cells. The survival of the Tasmanian devil, the largest marsupial carnivore, is threatened by two independent transmissible cancers, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a peptide vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to Major Histocompatibility Complex class I molecules from the Tasmanian devil and its transmissible tumours.

2021-02-08 | PXD020614 | Pride

The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer (small RNA sequencing)

Project description:The Tasmanian devil, a marsupial carnivore, is endangered due to the emergence of a clonally transmissible cancer known as Devil Facial Tumor Disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, mitochondrial genome analysis, as well as deep sequencing of the DFTD transcriptome and miRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor, and suggest that the disease is of Schwann cell origin. On the basis of these results we have generated a diagnostic marker for DFTD, and identify a suite of genes of relevance to DFTD pathology and transmission. We provide a genomic dataset for the Tasmanian devil, which is applicable to cancer diagnosis, disease evolution and conservation biology. This submission contains only small RNA sequence data from this study. Small RNA (18 - 24 nt) sequences from 15 Tasmanian devil (Sarcophilus harrisii) tissue samples

2010-01-01 | E-GEOD-18352 | biostudies-arrayexpress

Tasmanian Devil Facial Tumour Disease - Imiquimod treatment of DFT1 cells

Project description:A Tasmanian Devil Facial Tumour Disease (DFTD) tumor cell line was treated with the drug Imiquimod

2018-04-12 | PXD007135 | Pride

Sarcophilus harrisii

Project description:Tasmanian devil facial tumour 454 transcriptome

| PRJNA79479 | ENA

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Project description:The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the culprit molecular underpinnings, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, inhibition of ERBB blocked phosphorylation of STAT3 and arrested cancer cells. Blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC-I gene expression. This link between the hyperactive ERBB-STAT3 axis and decreased MHC-I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and lets us propose a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.

2019-01-18 | PXD009283 | Pride

The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer (small RNA sequencing)

2010-01-01 | GSE18352 | GEO

Tasmanian devil facial tumour-derived extracellular vesicles reveal mesenchymal transition markers and adhesion molecules related to metastasis.

Project description:The iconic Tasmanian devil (Sarcophilus harrisii) is endangered due to the transmissible cancer Devil Facial Tumour Disease (DFTD), of which there are two genetically independent subtypes (DFT1 and DFT2). While DFT1 and DFT2 can be differentially diagnosed using tumour biopsies, there is an urgent need to develop less invasive biomarkers that can detect DFTD and distinguish between subtypes. Extracellular vesicles (EVs), the nano-sized membrane-enclosed vesicles present in most biofluids, represent a valuable resource for biomarker discovery. Here, we characterized the proteome of EVs from cultured DFTD cells using data independent acquisition mass spectrometry and an in-house spectral library of >1,500 proteins. EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with focal adhesion functions. Furthermore, hallmark proteins of epithelial mesenchymal transition were enriched in DFT2 EVs relative to DFT1 EVs. These findings were validated in clinical samples, revealing that the mesenchymal marker tenascin-C was also enriched in EVs derived from the serum of devils infected with DFT2 relative to those infected with DFT1 and healthy controls. This first EV-based investigation of DFTD increases our understanding of the cancers’ EVs and their possible involvement in DFTD progression, such as metastasis. Finally, we demonstrated the potential of EVs to differentiate between DFT1 and DFT2 that highlights their potential use as less invasive liquid biopsies for the Tasmanian devil and other animals.

2024-05-22 | PXD025579 | Pride

DNA methylation profile of Tasmanian Devil facial tumor biopsies and matched healthy skin and spleen samples, as well as additional nerve tissue, and strain 1 tumor cell line.

Project description:Purpose: Depict the landscape of epigenetic regulation in Tasmanian devil facial tumor biopsies. Differential analysis of healthy versus tumor biopsies highlighted 166 candidate genes with different DNA methylation levels in their promoters, which included the tumor-specific hypermethylated promoters of Estrogen Receptor 1 (ESR1) and the transcription factor GATA3.

2019-01-14 | GSE108160 | GEO

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