Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD73 Immune Checkpoint Defines Inducible Regulatory NK cells in the Tumor Microenvironment

ABSTRACT: CD73 Immune Checkpoint Defines Inducible Regulatory NK cells in the Tumor Microenvironment

PROVIDER: PRJNA515273 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8445110_1.fastq.gz	Fastqsanger.gz
	SRR8445110_2.fastq.gz	Fastqsanger.gz
	SRR8445120_1.fastq.gz	Fastqsanger.gz
	SRR8445120_2.fastq.gz	Fastqsanger.gz
	SRR8445130_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 80

Similar Datasets

CD73 Immune Checkpoint Defines Inducible Regulatory NK cells in the Tumor Microenvironment

Project description:High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression. Elevated levels of CD73 has also been observed in patients who progress on anti–PD-1 immunotherapy. While regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known if conventional T cells and natural killer (NK) cells can express CD73. We found that the expression of CD73 is restricted to tumor-infiltrating NK cells and the frequency of these cells correlate with larger tumor size in patients with breast cancer. In addition, the expression of other immune checkpoint receptors including LAG-3 and VISTA was significantly higher in CD73 positive NK cells than on CD73 negative NK cells. Furthermore, the prognostic value of CD73 gene expression was influenced by NK cell signature expressed in patients with breast cancer and sarcoma. Mechanistically, upon engagement of 4-1BBL on tumor cells, NK cells transport CD73 in intracellular vesicles to the cell surface and extracellular space via actin polymerization-dependent exocytosis. These CD73 positive NK cells undergo transcriptional reprogramming and upregulate IL10 production via STAT3 transcriptional activity and suppress CD4 T cell activity. Altogether, our results support that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immune regulatory properties within the tumor microenvironment.

2020-06-10 | GSE125119 | GEO

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment.

Project description:High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.

| S-EPMC7269592 | biostudies-literature

CIS is a potent checkpoint in NK cell-mediated tumour immunity

Project description:Natural killer (NK) cells have evolved to detect and kill aberrant cells with this activity being governed by the cytokine interleukin (IL)-15 and foreign and self-ligands. We have identified CIS (Cytokine-inducible SH2-containing protein; Cish gene) as the critical negative regulator of IL-15 signalling in NK cells. Cish was rapidly induced in response to IL-15 and deletion of Cish rendered NK cells hypersensitive to IL-15, as evidenced by superior proliferation, survival, IFN-γ production and cytotoxicity towards tumours. This was associated with enhanced JAK/STAT signalling in Cish-deleted NK cells. Correspondingly, CIS interacted with the tyrosine kinase JAK1, inhibiting its enzymatic activity and targeting JAK for proteasomal degradation. Cish-/- mice were resistant to melanoma, prostate and breast cancer metastasis in vivo, and this was intrinsic to NK cell activity. This study has uncovered a potent checkpoint in NK cell-mediated tumour immunity and holds promise for novel immunotherapies directed at blocking CIS function.

2016-05-20 | GSE79409 | GEO

The SIRPα-CD47 immune checkpoint in NK cells

Project description:The SIRPα-CD47 immune checkpoint in NK cells

| PRJEB36016 | ENA

NK cell-derived GM-CSF is critical for enhancing pathological arthritis

Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.

2020-02-19 | PXD012794 | Pride

CD73 contributes to the pathogenesis of Fusion-Negative Rhabdomyosarcoma through the purinergic signaling pathway

Project description:We performed RNA-seq to evaluated the transcriptional changes of CD73 knockdown in RD cells, a Fusion Negative Rhabdomyosarcoma cell line. We used a Dox-inducible shRNA targetting the 3'UTR of CD73 to knockdown this gene. Cells with No-Dox were used as control.

2024-02-07 | GSE240722 | GEO

Expression data from CD73 positive adipose derived mesenchymal stem cells (CD73+ AD-MSCs) and CD73 negative adipose derived mesenchymal stem cells (CD73- AD-MSCs) of mouse

Project description:MSCs are a heterogeneous population and the specific population of MSCs may exhibit a selective ability for tissue repair. The aim of our research was to adapt the CD73+ subgroup of adipose derived MSCs (AD-MSCs) for the therapy of myocardial infarction (MI). Our results revealed that CD73+ AD-MSCs played more effective role in the acceleration function of cardiac recovery by promoting angiogenesis in a rat model of MI compared to mixed AD-MSCs and CD73- AD-MSCs. Microarray analysis shows differences between CD73+ and CD73- AD-MSCs when transcription profile of these two subgroups were compared, especially in VEGF pathway.

2021-06-02 | GSE167219 | GEO

IL-1R8 is a checkpoint in NK cells regulating anti-tumor and anti-viral activity

Project description:We reported that IL-1R8 serves as a checkpoint for NK cell maturation and effector functions. Its genetic blockade unleashes NK-cell mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis and cytomegalovirus infection.

2017-11-02 | GSE105043 | GEO

CD73+ CD127high long-term memory CD4 T cells are highly proliferative in response to recall antigens and are early targets in HIV-1 infection

Project description:HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4 T cells which highly express the alpha-chain of the receptor for IL-7 (CD127), but not CD38 or Ki-67 in vivo, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease early in HIV-1 infection. We compared gene expression profiles of healthy subjects recovered CD4+CD73+ to CD4+CD73- T cells, and also CD8+CD73+ to CD8+CD73- T cells

2021-02-02 | GSE160805 | GEO

CD73 knockdown effect in pancreatic cancer cell lines

Project description:Recent studies have shown that non-enzymatic function of CD73 play a key role in tumor progression, but this function of CD73 in pancreatic cancer cells has not been studied. In the present study, PANC-1 cell lines were transfected with CD73 siRNA, and proliferation ability and cell cycle was significantly inhibited. However, little is known about the mechanisms involved in CD73 regulation in tumors.

2018-07-13 | GSE117012 | 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