Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulatory T cells converted from T helper 1 cells in tumors suppress cancer immunity via CD39

ABSTRACT: Although Foxp3-expressing regulatory T (Treg) cells are widely believed to impede anti-tumor immunity, their regulation and functional mechanisms are not well understood. Here, through characterization of multiple cancer models, we identified substantial periphery-induced Treg cells in the tumor microenvironment, depletion of which provoked anti-tumor responses and conferred potent therapeutic effects by increasing CD8+ T cell numbers and cytolytic function. Through fate-mapping and transfer experiments, we found IFN-γ-expressing T helper (Th) 1 cells developed into Treg cells in tumors, in response to TGF-β signaling. Hence, tumor-resident Treg cells highly expressed T-bet, which was essential for their development and function. CD39, highly expressed by T-bet+ Treg cells in both mouse and human tumors, is required for Treg suppression of CD8+ T cell response. In summary, our study has elucidated a developmental pathway of intra-tumoral Treg cells and implicated new ways of targeting them in cancer patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE240961 | GEO | 2024/02/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulatory T cells converted from T helper 1 cells in tumors suppress cancer immunity via CD39

Project description:Although regulatory T (Treg) cells are widely believed to impede anti-tumor immunity, their regulation and functional mechanisms are not well understood. Here, through characterization of multiple cancer models, we identified substantial periphery-induced Treg cells in the tumor microenvironment (TME), depletion of which provoked anti-tumor responses and conferred potent therapeutic effects by increasing functional CD8+ T cells. Through fate-mapping and transfer experiments, we found IFN-γ-expressing T helper (Th) 1 cells developed into Treg cells in tumors, in response to TGF-β signaling. Pseudotime trajectory further revealed the terminal differentiation of Th1-like Treg cells from Th1 cells in the TME. Hence, tumor-resident Treg cells highly expressed T-bet, which was essential for their function in the TME. CD39, highly expressed by T-bet+ Treg cells in both mouse and human tumors, is required for Treg suppression of CD8+ T cell response. In summary, our study has elucidated a developmental pathway of intra-tumoral Treg cells and implicated new ways of targeting them in cancer patients.

2024-12-16 | GSE283943 | GEO

Profiling of lung tumor-infiltrating CD8 T cells according to their expression status of CD39

Project description:Human tumors are infiltrated by various immune cells, including CD8 T cells. CD8 T cells express unique receptors that can recognize peptides at the host’s cells, including tumor cells. After probing the antigen specificity of ex-vivo tumor-infiltrating CD8 T cells from human tumors, we hypothesized that expression of CD39 was correlated with tumor-specificity. The present experiment aims at better characterizing ex-vivo CD39+ vs CD39- CD8 T cells.

2018-05-17 | GSE113588 | GEO

Profiling of colorectal tumor-infiltrating CD8 T cells according to their expression status of CD39

2018-05-17 | GSE113585 | GEO

CD39 expression identifies terminally exhausted CD8+ T cells

Project description:Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. CD8+ T cells from subjects with HCV infection were sorted and pelleted and re-suspended in TRIzol (Invitrogen). RNA extraction was performed using the RNAdvance Tissue Isolation kit (Agencourt). Concentrations of total RNA were determined with a Nanodrop spectrophotometer or Ribogreen RNA quantification kits (Molecular Probes/Invitrogen). RNA purity was determined by Bioanalyzer 2100 traces (Agilent Technologies). Total RNA was amplified with the WT-Ovation Pico RNA Amplification system (NuGEN) according to the manufacturer's instructions. After fragmentation and biotinylation, cDNA was hybridized to HG-U133A 2.0 microarrays (Affymetrix).

2015-09-08 | E-GEOD-72752 | biostudies-arrayexpress

RNA-Seq of FACS-sorted, KIR-CD39-,KIR+CD39- and KIR+CD39+, Uterine NK cells (uNK cells) from human decidual samples

Project description:Uterine NK cells (uNK cells) form a distinct immune cell population in the endometrium and decidua. Here, we FACS-sorted KIR-CD39-,KIR+CD39- and KIR+CD39+ uNK cells from decidual samples.

2021-02-19 | E-MTAB-8709 | biostudies-arrayexpress

CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [VDJ]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

2022-11-17 | GSE218261 | GEO

CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [scRNA]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

2022-11-17 | GSE218258 | GEO

CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [FB]

Project description:We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

2022-11-17 | GSE218259 | GEO

CD39 expression identifies terminally exhausted CD8+ T cells

2015-09-08 | GSE72752 | GEO

A Population of Tumor-Infiltrating CD4+ T-cells Co-expressing CD38 and CD39 is Associated with Checkpoint Inhibitor Resistance

Project description:We previously showed that elevated peripheral blood frequencies of a population of T-cells defined by the marker set CD3+CD4+CD127-GARP-CD38+CD39+ were associated with checkpoint immunotherapy resistance in metastatic melanoma patients. In this study we sought to further understand the role(s) of this population of ectoenzyme expressing T-cells (Teee). Using RNA-sequencing and flow cytometry to evaluate Teee from the peripheral blood of metastatic melanoma patients, we found that Teee were proliferative, apoptotic, had exhaustion associated phenotypes, and had high expression of inhibitory molecules. Co-culture of patient Teee with autologous T-cells in vitro resulted in suppression of proliferation of the target T-cells. Using single-cell RNA-sequencing datasets, we identified distinct clusters of cells with a Teee gene signature present in melanoma, non-small cell lung cancer and bladder cancer patients’ tumors. Teee were not present in healthy bladder tissue. Using multispectral immunofluorescence of melanoma patient FFPE tumor samples, we were able to identify CD4+ T-cells co-expressing CD38 and CD39 in the tumor microenvironment, which preferentially associated with Ki67- CD8+ T-cells. Finally, we found that high baseline intra-tumor frequencies of cells with a Teee gene signature were associated with checkpoint immunotherapy resistance and poor overall survival in metastatic melanoma patients. These results build upon our previous findings, demonstrating that a novel population of CD4+ T-cells co-expressing CD38 and CD39 are found in the periphery and tumor of patients and are associated with checkpoint immunotherapy resistance.

2023-07-17 | GSE224099 | 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