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

ABSTRACT: An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer

PROVIDER: PRJNA531099 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8858560.fastq.gz	Fastqsanger.gz
	SRR8858570.fastq.gz	Fastqsanger.gz
	SRR8858580.fastq.gz	Fastqsanger.gz
	SRR8858590.fastq.gz	Fastqsanger.gz
	SRR8858600.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 54

Similar Datasets

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

2019-09-28 | GSE129381 | GEO

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

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

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

| PRJNA531104 | ENA

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

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

| PRJNA531105 | ENA

Activated SUMOylation restricts the MHC class I antigen presentation pathway to confer immune evasion in cancer

Project description:Activated SUMOylation is a hallmark of aggressive cancers. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionary conserved function of activated SUMOylation, which attenuates the immunogenicity of tumor cells. Activated SUMOylation allows cancer cells to evade CD8+ T-cell immunosurveillance by repressing the MHC-I antigen processing and presentation machinery (APM). While loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, the pharmacological inhibition of SUMOylation (SUMOi) restored the expression of the MHC-I APM and enhanced the susceptibility of tumor cells to CD8+ T-cell mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T-cells itself and thereby drives a feed-forward loop amplifying the specific anti-tumor immune response. In summary, we show that activated SUMOylation converts tumor cells into a state of immune evasion, and identify SUMOi as rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies.

2022-01-15 | PXD030506 | Pride

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Project description:Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced 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 MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.

| S-EPMC6876280 | biostudies-literature

Mal2 drives immune evasion by reducing antigen presentation on tumor cells

Project description:Current cancer immunotherapies are assumed to improve infiltration and cytotoxicity of immune cells in the tumor. However, tumor cells have developed a variety of resistance mechanisms to suppress the MHC class I antigen presentation, and thereby impair the cytotoxicity of CD8+ T cells. Here, we identified Mal2 as a key player that mediates the turnover of the antigen-MHC-I complex and reduce the antigen presentation on tumor cells. Mal2 promotes the endocytosis of tumor antigen via direct interaction with the MHC-I complex and endosome-associated Rab5/7. In mouse and human breast tumor models, inhibition of Mal2 profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that Mal2 is a potential target for breast cancer immunotherapy.

2020-01-23 | GSE144099 | GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-09-28 | GSE129382 | GEO

Cathepsin D-Mediated MHC-I Degradation Contributes to Immune Evasion in Microsatellite Stable Colorectal Cancer

Project description:Microsatellite stable (MSS) colorectal cancer (CRC) is often characterized as a "cold" tumor, exhibiting minimal responsiveness to monotherapy with PD-1 antibodies. The underlying mechanisms of this intrinsic unresponsiveness to immunotherapy have been elusive. Here, we report that cathepsin D (CTSD) is highly expressed in MSS CRC, significantly contributing to its resistance to immunotherapy. Specifically, CTSD facilitates immune evasion by shielding cancer cells from cytotoxic T-cell-mediated killing. Mechanistically, as a protease, CTSD interacts with the α2 domain of the major histocompatibility complex class I (MHC-I) molecule via its catalytic domain's light chain, promoting the degradation of MHC-I through lysosomal pathways and disrupting the recycling of MHC-I to the cell surface. Notably, deletion or pharmacological inhibition of CTSD with pepstatin A prevents this immune evasion and enhances the efficacy of anti-PD-1 antibodies. Collectively, these findings highlight the role of CTSD in immune evasion and provide a compelling rationale for the development of a novel combination therapy involving CTSD inhibition and anti-PD-1 immunotherapy in CRC.

2025-10-18 | GSE306871 | GEO

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Project description:A progressive increase in the breadth and specificity of autoantibodies over time, termed epitope spreading, drives pathogenic targeting of an ever-widening repertoire of self-components in many autoimmune diseases. Ostensibly, this progressive inclusion of additional B cell clones into an ongoing autoreactive response can occur through linked recognition, whereby proto-autoreactive B cells recognize distinct antigenic epitopes, which carry shared T cell epitopes. In a murine model displaying epitope spreading resembling that observed in systemic lupus erythematosus, we find that the epitope spreading process is compartmentalized by MHC. Antigen presentation by B cells carrying two MHC haplotypes can bridge the MHC barrier between two compartments of B cells that do not share MHC haplotypes, by communicating with two separate pools of MHC-restricted T cells. This leads to inclusion of distinct and diverse B cell reactivities in germinal centers. Our findings demonstrate a formidable capacity of B cells to drive the autoreactive response.

2022-07-01 | GSE202358 | 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