Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Eomes sustains progenitor CD4⁺ T helper cells to promote anti-tumor immunity during immunotherapy [scRNA]

ABSTRACT: CD4⁺ T helper (Th) cells contribute to tumor immunity, yet the subsets and differentiation programs involved remain unclear. Here, we show that the transcription factor Eomesodermin (Eomes) is essential for Th–mediated anti-tumor immunity by orchestrating the differentiation and maintenance of an exhausted-like Th cell lineage, which is transcriptionally and functionally distinct from conventional effector or memory Th subsets. This Eomes-dependent program is further enhanced by 4-1BB stimulation, promoting effective Th cell–mediated tumor control. The precursor subset of this lineage (pTh) expresses stemness-associated transcription factors, displays self-renewal capacity, and can differentiate into effector cells capable of controlling tumor growth. At the transcriptional level, Eomes supports the survival, metabolic fitness, and apoptotic resistance of this lineage. Notably, Eomes⁺ pTh cells are directly relevant to human cancer, being detected across multiple tumor types, exhibiting conserved transcriptional features, and representing the most expanded Th cell population upon immune checkpoint blockade therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE324687 | GEO | 2026/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming

Project description:Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.

2019-06-06 | PXD014142 | Pride

Gene expression of sorted Eomes+ and Eomes‒ γδ T cells from spleen of Eomes-IRES-GFP mice.

Project description:Eomesodermin (Eomes) is a transcription factor with a crucial role regulating cytotoxic function, development and survival of immune cells. Although it is known that γδ T cells can express Eomes, its function on those cells is still largely unknown. Using Eomes-IRES-GFP mice we were able to sort for Eomes+ and Eomes‒ γδ T cells populations and get their gene expression profiles, bringing light to the role of Eomes on γδ T cells.

2017-04-10 | GSE85585 | GEO

Expression data from Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment

Project description:Development, maturation, and function of CD8 T cells is regulated by transcription factor expression. Expression of the transcription factor Eomesodermin was found to be significantly increased in CD8 T cells following aOX40/aCTLA-4 immunotherapy in mice. We used microarray analysis to detail gene expression in Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment to determin functional differences between these two populations.

2021-02-11 | GSE166532 | GEO

Differential requirement for Nfil3 during NK cell development

Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets

2014-05-07 | E-GEOD-54291 | biostudies-arrayexpress

A comparison of the transcriptional profiles of invariant NKT cells derived from Wild type and Eomes conditional knockout mice

Project description:Functional subsets of iNKT cells, NKT1, NKT2 and NKT17, have been reported to arise during the thymus to peripheral differentiation stages. The key transcription factors for NKT1, NKT2 and NKT17 development in the thymus have been identified as T-bet, Gata3 and Rorγt, respectively. In contrast, these iNKT cell subsets can also undergo further differentiation in the periphery. Eomesodermin (Eomes) is a T-box transcription factor with high homology to T-bet and is expressed by activated CD8+ T cells as well as in resting and activated NK cells. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. Eomes regulates the differentiation of NKT1 cells in the thymus. In the peripheral tissue, Klrg1+ iNKT1 cells are generated in lung after vaccination with -GalCer-pulsed DCs (DC/Gal) as memory like iNKT cells. In the current study, we found that Eomes also regulates their differentiation into memory-like KLRG1+iNKT cells in the periphery.

2019-05-09 | GSE128069 | GEO

EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (ChIP-Seq)

Project description:Memory CD8 T cells have a unique ability to provide lifelong immunity against pathogens. Although memory features generally arise after a challenge with foreign antigen, naïve CD8 single positive (SP) thymocytes may already acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these “innate memory” CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming was secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, we identified direct interaction between EOMES and BRG1 and showed that in vivo acquisition of EOMES-dependent program by CD8SP thymocytes was dependent on this chromatin remodeling factor. In conclusion, our results support a strong epigenetic basis for EOMES-driven establishment of CD8 T cell unconventional memory program.

2019-06-06 | GSE124912 | GEO

EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (ATAC-Seq)

2019-06-06 | GSE124911 | GEO

EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (RNA-Seq)

2019-06-06 | GSE124913 | GEO

Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells

Project description:The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN-g and represses alternative cell fates like Th2 and Th17. T-bet’s paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells can mostly be found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we show in a novel genetic model that the expression of Eomes in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes was sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promoted a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset with the potential to limit inflammation and immunopathology as well as to eliminate antigen-presenting and malignant cells.

2023-01-19 | GSE213980 | GEO

The molecular basis of specific functions of Brachyury and Eomes for mesoderm and endoderm lineage specification

Project description:The Tbx factors Eomesodermin (Eomes) and Brachyury instruct endoderm and mesoderm specification. Both Tbx factors have common large overlap in chromatin binding sites, however their embryonic phenotypes of mutants largely differ. In this study, we delineate the distinct binding patterns and gene target sets of Eomes and Brachyury providing a molecular model of distinct fate specification programs.

2023-07-26 | GSE194192 | 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