Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay

ABSTRACT: Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay

PROVIDER: PRJNA1021613 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	SRR26199833_1.fastq.gz	Fastqsanger.gz
	SRR26199833_2.fastq.gz	Fastqsanger.gz
	SRR26199835_1.fastq.gz	Fastqsanger.gz
	SRR26199835_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 45

Similar Datasets

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scRNA-seq]

Project description:Epigenetic regulation drives the differentiation of T cells into phenotypically stable subsets including a dysfunctional state termed exhaustion, the presence of these epigenetically distinct T cells in tumors make them non-responsive to checkpoint blockade. Cancer immunotherapies restoring T cell function have transformed cancer treatment by preventing immune evasion of tumor cells allowed by T cell exhaustion. However, some patients develop resistance to immunotherapy or do not respond. Recent literature has demonstrated that epigenetic regulation governs the transition from effector to exhausted T cells. Here, we describe a novel antigen-specific assay for T-cell exhaustion that produces T cells biologically and epigenetically similar to their in vivo exhausted counterpart. We perform a CRISPR KO screen for epigenetic regulators of the human genome and validate Ikaros as a driver of T-cell exhaustion. We determined that the Ikaros degrader iberdomide prevents exhaustion by blocking chromatin remodeling at T cell effector enhancers by preserving activity of key transcription factors AP-1, NF-κB and NFAT using transcription factor footprinting analysis. Thus, our study uncovers a role for Ikaros, degraded by the drug iberdomide, as a driver of T-cell exhaustion.

2024-09-02 | GSE244180 | GEO

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scATAC-seq]

2024-09-02 | GSE244162 | GEO

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [bulk ATAC-seq]

2024-09-02 | GSE244183 | GEO

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scATAC-seq]

Project description:Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scATAC-seq]

| PRJNA1021606 | ENA

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scRNA-seq]

Project description:Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [scRNA-seq]

| PRJNA1021609 | ENA

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [bulk ATAC-seq]

Project description:Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay [bulk ATAC-seq]

| PRJNA1021618 | ENA

Degradation of Ikaros prevents epigenetic progression of T cell exhaustion in novel antigen-specific assay

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

2024-09-02 | GSE244184 | GEO

Degradation of IKZF1 prevents epigenetic progression of T cell exhaustion in an antigen-specific assay.

Project description:In cancer, chronic antigen stimulation drives effector T cells to exhaustion, limiting the efficacy of T cell therapies. Recent studies have demonstrated that epigenetic rewiring governs the transition of T cells from effector to exhausted states and makes a subset of exhausted T cells non-responsive to PD1 checkpoint blockade. Here, we describe an antigen-specific assay for T cell exhaustion that generates T cells phenotypically and transcriptionally similar to those found in human tumors. We perform a screen of human epigenetic regulators, identifying IKZF1 as a driver of T cell exhaustion. We determine that the IKZF1 degrader iberdomide prevents exhaustion by blocking chromatin remodeling at T cell effector enhancers and preserving the binding of AP-1, NF-κB, and NFAT. Thus, our study uncovers a role for IKZF1 as a driver of T cell exhaustion through epigenetic modulation, providing a rationale for the use of iberdomide in solid tumors to prevent T cell exhaustion.

| S-EPMC11604474 | biostudies-literature

LKB1 prevents ILC2 exhaustion and lung cancer metastasis

Project description:LKB1 prevents ILC2 exhaustion and lung cancer metastasis

| PRJNA861294 | ENA

Ikaros prevents autoimmunity by promoting anergy induction and restraining Toll-like receptor signaling in B cells

Project description:Establishment of a diverse B-cell receptor (BCR) repertoire by V(D)J recombination generates autoreactive B-cells that are eliminated by central tolerance in the bone marrow or down-regulate their BCR responsiveness to self-antigen during anergy induction in peripheral B-cells. The loss of anergy combined with hyperactivation of nucleic acid-sensing Toll-like receptors (TLRs) is thought to break B-cell tolerance leading to autoimmunity, although the transcriptional factors controlling these processes are still unknown. Here, we describe a critical role of Ikaros in promoting B-cell anergy and restraining TLR signaling by analyzing mice with specific deletion of Ikaros in mature B-cells, which resulted in systemic autoimmunity. While regulating many anergy-associated genes, Ikaros also activated the Zfp318 gene, implicated in down-tuning of the BCR responsiveness by shifting expression from IgM to IgD in anergic B-cells. TLR signaling was hyperactive in Ikaros-deficient B-cells, which failed to up-regulate feedback inhibitors of the MyD88-NF-?B signaling pathway. Systemic inflammation was lost upon expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B-cells, which identified Ikaros as a guardian preventing autoimmunity by coordinately regulating anergy induction and TLR signaling.

2019-07-01 | GSE122313 | 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