Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion

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

ORGANISM(S): Mus musculus

PROVIDER: GSE130540 | GEO | 2019/05/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion.

Project description:T cells expressing chimeric antigen receptors (CAR T cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they have not been as effective against solid tumors because they become hyporesponsive ("exhausted" or "dysfunctional") within the tumor microenvironment, with decreased cytokine production and increased expression of several inhibitory surface receptors. Here we define a transcriptional network that mediates CD8+ T cell exhaustion. We show that the high-mobility group (HMG)-box transcription factors TOX and TOX2, as well as members of the NR4A family of nuclear receptors, are targets of the calcium/calcineurin-regulated transcription factor NFAT, even in the absence of its partner AP-1 (FOS-JUN). Using a previously established CAR T cell model, we show that TOX and TOX2 are highly induced in CD8+ CAR+ PD-1high TIM3high ("exhausted") tumor-infiltrating lymphocytes (CAR TILs), and CAR TILs deficient in both TOX and TOX2 (Tox DKO) are more effective than wild-type (WT), TOX-deficient, or TOX2-deficient CAR TILs in suppressing tumor growth and prolonging survival of tumor-bearing mice. Like NR4A-deficient CAR TILs, Tox DKO CAR TILs show increased cytokine expression, decreased expression of inhibitory receptors, and increased accessibility of regions enriched for motifs that bind activation-associated nuclear factor ?B (NF?B) and basic region-leucine zipper (bZIP) transcription factors. These data indicate that Tox and Nr4a transcription factors are critical for the transcriptional program of CD8+ T cell exhaustion downstream of NFAT. We provide evidence for positive regulation of NR4A by TOX and of TOX by NR4A, and suggest that disruption of TOX and NR4A expression or activity could be promising strategies for cancer immunotherapy.

| S-EPMC6589758 | biostudies-literature

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [ATAC-Seq]

Project description:We comapre mRNA expression level TOX and TOX2 CAR TILS and WT CAR TILs

2019-05-31 | GSE130539 | GEO

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

Project description:We comapre mRNA expression level TOX and TOX2 CAR TILS and WT CAR TILs

2019-05-31 | GSE130538 | GEO

CD4+ T cells in classical Hodgkin lymphoma express exhaustion associated transcription factors TOX and TOX2: Characterizing CD4+ T cells in Hodgkin lymphoma.

Project description:In classical Hodgkin lymphoma (cHL), the highly abundant CD4+ T cells in the vicinity of tumor cells are considered essential for tumor cell survival, but are ill-defined. Although they are activated, they consistently lack expression of activation marker CD26. In this study, we compared sorted CD4+CD26- and CD4+CD26+ T cells from cHL lymph node cell suspensions by RNA sequencing and T cell receptor variable gene segment usage analysis. This revealed that although CD4+CD26- T cells are antigen experienced, they have not clonally expanded. This may well be explained by the expression of exhaustion associated transcription factors TOX and TOX2, immune checkpoints PDCD1 and CD200, and chemokine CXCL13, which were amongst the 100 significantly enriched genes in comparison with the CD4+CD26+ T cells. Findings were validated in single-cell RNA sequencing data from an independent cohort. Interestingly, immunohistochemistry revealed predominant and high frequency of staining for TOX and TOX2 in the T cells attached to the tumor cells. In conclusion, the dominant CD4+CD26- T cell population in cHL is antigen experienced, polyclonal, and exhausted. This population is likely a main contributor to the very high response rates to immune checkpoint inhibitors in cHL.

| S-EPMC8803106 | biostudies-literature

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion

Project description:Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion

| PRJNA540587 | ENA

BLIMP1 and NR4A3 Transcription Factors Reciprocally Regulate Antitumor CAR T-cell Stemness and Exhaustion

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

2022-08-04 | GSE210265 | GEO

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

Project description:Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

| PRJNA540585 | ENA

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [ATAC-Seq]

Project description:Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [ATAC-Seq]

| PRJNA540590 | ENA

Nr4a transcription factors limit CAR-T cell function in solid tumors

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

2019-02-13 | GSE123739 | GEO

Dynamic chromatin regulatory landscape of human CAR T cell exhaustion

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

2021-05-01 | GSE168882 | 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