Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cytotoxic Innate Lymphoid Cells Sense Cancer Cell-Expressed Interleukin-15 to Suppress Human and Murine Malignancies

ABSTRACT: Malignancy can be suppressed by the immune system. However, the classes of immunosurveillance responses and their mode of tumor sensing remain incompletely understood. Here, we show that while clear cell renal cell carcinoma (ccRCC) was infiltrated by exhaustion-phenotype CD8+ T cells which negatively correlated with patient prognosis, chromophobe RCC had abundant infiltration of granzyme A-expressing intraepithelial type 1 innate lymphoid cells (ILC1s) that positively associated with patient survival. Interleukin-15 (IL-15) promoted ILC1 granzyme A expression and cytotoxicity, and IL-15 expression in chRCC tumor tissue positively tracked with the ILC1 response. An ILC1 gene signature also predicted survival of a subset of breast cancer patients in association with IL-15 expression. Notably, ILC1s directly interacted with cancer cells, and IL-15 produced by cancer cells supported the expansion and anti-tumor function of ILC1s in a murine breast cancer model. Thus, ILC1 sensing of cancer cell IL-15 defines an immunosurveillance mechanism of epithelial malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199798 | GEO | 2022/04/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cytotoxic Granzyme C Expressing ILC1s Contribute to Antitumor Immunity and Neonatal Autoimmunity

Project description:Innate lymphocytes are integral components of the cellular immune system that coordinates host defense against a multitude of challenges and can trigger immunopathology when dysregulated. Natural killer (NK) cells and innate lymphoid cells (ILCs) are innate immune effectors postulated to functionally mirror conventional cytotoxic T lymphocytes and helper T cells, respectively. Here, we show that the cytolytic molecule granzyme C was surprisingly expressed in cells with the phenotype of type 1 ILCs (ILC1s) in mouse liver and salivary gland. Cell fate-mapping and transfer studies revealed that granzyme C-expressing innate lymphocytes could be derived from ILC progenitors and did not interconvert with NK cells, ILC2s, or ILC3s. Granzyme C defined a maturation state of ILC1s, which required the transcription factor T-bet and to a lesser extent Eomes specifically in the salivary gland for their maintenance. Furthermore, transforming growth factor-b (TGF-b) signaling promoted maintenance of granzyme C-expressing ILC1s in the salivary gland and in the tumor of a transgenic breast cancer model, and their depletion caused accelerated tumor growth. ILC1s gained granzyme C expression following interleukin-15 (IL-15) stimulation, which enabled perforin-mediated cytotoxicity. Strikingly, constitutive activation of the IL-15-regulated transcription factor Stat5 in granzyme C-fate-mapped ILC1s triggered lethal perforin-dependent autoimmunity in neonatal mice. Thus, granzyme C marks a cytotoxic effector state of ILC1s, broadening their function beyond ‘helper-like’ lymphocytes.

2022-02-18 | GSE196716 | GEO

Microarray data from human cultured ILC3s

Project description:Innate lymphoid cells (ILCs) are tissue-resident lymphocytes subdivided into ILC1s, ILC2s and ILC3s based on core regulatory programs and signature cytokines secreted. ILCs exhibit functional plasticity: for instance, human IL-22-producing ILC3s convert into IFN-γ-producing ILC1-like in vitro. Whether this conversion occurs in vivo is unclear. Using flow cytometry, mass cytometry and scRNAseq, here we found that ILC3s and ILC1s occupy opposite ends of a spectrum including discrete subsets in human tonsils. RNA velocity suggested strong directionality toward ILC1s for one ILC3-ILC1 intermediate cluster. Clonal analysis revealed graded ability of ILC3-ILC1 subsets to convert into ILC1-like cells. When examined in humanized mice, ILC3 acquisition of ILC1 features showed tissue-dependency. In chromatin studies, Aiolos emerged as a nuclear factor that cooperates with Tbet to repress evolutionarily conserved regulatory elements active in ILC3s. The human intestine also exhibited an ILC3–ILC1 transitional population. We conclude that conversion of ILC3s to ILC1-like occurs in vivo in human tissues, and that tissue factors and Aiolos are crucial for this process.

2019-06-18 | GSE132843 | GEO

Microarray data from human ILC transitional populations

2019-05-07 | GSE130773 | GEO

Genome Wide Chromatin Mapping of Aiolos accessability and H3K27ac histone modifications in transfected MNK3 cells

2019-05-07 | GSE130774 | GEO

RNA-Seq from human ILC transitional populations

2019-05-07 | GSE130772 | GEO

scRNASeq of human innate lymphoid cells from different compartments

Project description:Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identifiy a population of Ã¢Â€Âœliver-typeÃ¢Â€Â ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s were CD49a+CD94+CD200R1+, expressed the transcription factor T-BET, do not express the activating receptor NKp80, or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-ÃŽÂ³, TNF-ÃŽÂ±, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme B. Liver- type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ÃŽÂ²1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

| EGAS00001006847 | EGA

scRNAseq of human blood, tonsil, lung and small intestine innate lymphoid cells

Project description:Group 1 innate lymphoid cells (ILC1s) are cytotoxic and interferon gamma-producing lymphocytes lacking antigen-specific receptors, which include ILC1s and natural killer (NK) cells. In mice, ILC1s differ from NK cells, as they develop independently of the NK-specifying transcription factor EOMES, while requiring the repressor ZFP683 (ZNF683 in humans) for tissue residency. Here we identify highly variable ILC1 subtypes across tissues through investigation of human ILC1 diversity by single-cell RNA sequencing and flow cytometry. The intestinal epithelium contained abundant mature EOMES− ILC1s expressing PRDM1 rather than ZNF683, alongside a few immature TCF7+PRDM1− ILC1s. Other tissues harbored NK cells expressing ZNF683 and EOMES transcripts; however, EOMES protein content was variable. These ZNF683+ NK cells are tissue-imprinted NK cells phenotypically resembling ILC1s. The tissue ILC1-NK spectrum also encompassed conventional NK cells and NK cells distinguished by PTGDS expression. These findings establish a foundation for evaluating phenotypic and functional changes within the NK-ILC1 spectrum in diseases.

2024-06-14 | GSE240441 | GEO

SMAD4 impedes conversion of NK cells into ILC1-like cells by curtailing non-canonical TGFb signaling (human data sets)

Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to compare the transcriptional differences between human blood NK cells. NK cells from a patient with a deleterious SMAD4 mutation or control NK cells were cultured overnight with either IL-2 alone or TGFb1 and IL-2.

2017-07-31 | GSE100246 | GEO

Heterogeneity of liver group 1 ILC1s

Project description:RNA sequencing demonstrated that liver Ly49E+ and Ly49E- ILC1s exhibited unique transcriptional profiles and phenotypic features. scRNA-seq analysis revealed heterogeneity within both cNK and ILC1 subsets in liver. cNK cells could be further divided into three clusters, which corresponded to different developmental stages. Ly49E expression could dissect ILC1s into two subsets: Ly49E+ ILC1s and Ly49E- ILC1s, which exhibited different functional characteristics.

2022-03-27 | GSE171851 | GEO

Identification of human cytotoxic ILC3s

Project description:Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.

2020-09-14 | GSE147231 | 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