Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [scRNA-seq]

ABSTRACT: NK cells are innate lymphoid cells that protect the host against malignant and infected cells. Activation with the cytokines IL-12, IL-15, and IL-18 induces NK cells to differentiate into memory-like NK cells that have enhanced function compared to conventional NK (cNK) cells. However, mechanisms governing their biology and whether all cNK cells become memory-like are unclear. We identified that IL-12/15/18 activation results in two main fates: reprogramming into enriched memory-like (eML) or priming into effector (eff)cNK cells. eML NK cells have distinct epigenetics, phenotype, and enhanced function (IFNγ, cytotoxicity) compared to cNK and effcNK cells. In contrast, effcNK cells transcriptionally and epigenetically resemble cNK cells. Furthermore, we identify that within cNK cells CD56bright and CD56dim NK cells are the origin of distinct subsets of eML NK cells. Moreover, these two subsets of eML NK cells persist within patients receiving ML NK cell therapy for several months. Thus, IL-12/15/18 activation of NK cells results in multiple cell fates, with epigenetic and transcriptional mechanisms orchestrating eML NK cell differentiation and function. These mechanistic insights provide new strategies to enhance NK cellular therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264694 | GEO | 2024/06/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [CITE-seq]

Project description:NK cells are innate lymphoid cells that protect the host against malignant and infected cells. Activation with the cytokines IL-12, IL-15, and IL-18 induces NK cells to differentiate into memory-like NK cells that have enhanced function compared to conventional NK (cNK) cells. However, mechanisms governing their biology and whether all cNK cells become memory-like are unclear. We identified that IL-12/15/18 activation results in two main fates: reprogramming into enriched memory-like (eML) or priming into effector (eff)cNK cells. eML NK cells have distinct epigenetics, phenotype, and enhanced function (IFNγ, cytotoxicity) compared to cNK and effcNK cells. In contrast, effcNK cells transcriptionally and epigenetically resemble cNK cells. Furthermore, we identify that within cNK cells CD56bright and CD56dim NK cells are the origin of distinct subsets of eML NK cells. Moreover, these two subsets of eML NK cells persist within patients receiving ML NK cell therapy for several months. Thus, IL-12/15/18 activation of NK cells results in multiple cell fates, with epigenetic and transcriptional mechanisms orchestrating eML NK cell differentiation and function. These mechanistic insights provide new strategies to enhance NK cellular therapy.

2024-06-28 | GSE264696 | GEO

Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [ATAC-seq]

2024-06-28 | GSE264693 | GEO

A fusion protein complex that combines IL12, IL15, and IL18 signaling to induce memory-like NK cells for cancer immunotherapy

Project description:NK cells are a promising cellular therapy for cancer, with challenges in the field including persistence, functional activity, and tumor recognition. Briefly priming blood NK cells with rhIL-12, rhIL-15, and rhIL-18 (12/15/18) results in memory-like NK cell differentiation and enhanced responses against cancer. We developed a novel platform centered upon an inert tissue factor scaffold for production of heteromeric fusion protein complexes (HFPC). The first use of this platform combined IL-12, IL-15 and IL-18 receptor engagement (HCW9201) and the second adds CD16 engagement (HCW9207). HCW9201 and HCW9207 stimulated activation and proliferation signals in NK cells, but HCW9207 had decreased IL-18 receptor signaling. RNAseq and multidimensional mass cytometry revealed strong parallels between HCW9201 and 12/15/18. Moreover, HCW9201 stimulation improved NK cell metabolic fitness, and resulted in the DNA methylation remodeling characteristic of memory-like differentiation. HCW9201- and 12/15/18-primed similar increases in short-term and memory-like NK cell cytotoxicity and IFN-g production against leukemia targets, as well as equivalent control of leukemia in NSG mice. Thus, HFPCs represent a protein engineering approach that solves many problems associated with multi-signal receptor engagement on immune cells, and HCW9201-primed NK cells will be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.erm and memory-like NK cell cytotoxicity and IFN-g production against leukemia targets, as well as equivalent control of leukemia in NSG mice. Thus, HFPCs represent a protein engineering approach that solves many problems associated with multi-signal receptor engagement on immune cells, and HCW9201-primed NK cells will be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.

2021-04-15 | GSE172100 | GEO

RNA squencing of human NK cells activated with IL-15 or IL-12, IL-15, and IL-18

Project description:NK cells are an emerging cancer cellular therapy and potent mediators of anti-tumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in acute myeloid leukemia (AML) patients. However, the dynamic molecular changes that occur after memory-like differentiation in vitro are unclear. Here, control or ML NK cells purified from normal donor PBMC were generated in vitro. Briefly, RosetteSep-purified NK cells were incubated in IL-12, IL-15, and IL-18, or low-dose IL-15 as a control for 16-18 hours. Control or cytokine-activated NK cells were washed three times and cultured for 6 days in low-dose IL-15, which is required for NK cell survival. After 6 days, RNA was isolated from control and memory-like (ML) NK cells (IL12/15/18 activation) and RNA-sequencing performed. Because the transcription factor GATA-3 was increased specifically in ML NK cells, we hypothesized ML NK cells would exhibit a GATA-3 gene signature compared to control NK cells. Indeed, using GSEA, a significant gene signature was associated with ML NK cell differentiation. These data support the role for GATA-3 in regulating the ML NK cell molecular program.

2020-08-25 | GSE154694 | GEO

RNA squencing of human NK cells activated with IL-15, a combination of IL-12, IL-15, and IL-18, or with a trimeric fusion protein 18/12/TxM

Project description:Gene expression analysis of human NK cells at baseline, Day 1, and Day 6 after activation with IL-15, IL-12/15/18, or the 18/12/TxM molecule

2022-02-02 | GSE166268 | GEO

IL-15-DEPENDENT IMMUNE CROSS-TALK BETWEEN NK CELLS AND DENDRITIC CELLS IN HIV-1 ELITE CONTROLLERS [CUT&RUN]

Project description:As the principal effector cell population of the innate immune system, NK cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory epigenetic chromatin features, we here demonstrate that cytotoxic NK (cNK) cells from elite controllers (ECs) frequently display elevated activating histone modifications at the IL-2/IL-15 receptor β chain and the BCL-2 gene loci. These epigenetic changes translated into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincided with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these two innate immune cell populations resulted in improved IL-15-dependent cNK cell survival, paired with a metabolic profile biased towards IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display an epigenetically-programmed IL-15 response signature, and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.

2023-12-06 | GSE232915 | GEO

IL-15-DEPENDENT IMMUNE CROSS-TALK BETWEEN NK CELLS AND DENDRITIC CELLS IN HIV-1 ELITE CONTROLLERS [RNA-seq]

2023-12-06 | GSE232914 | GEO

NK-cell derived extracellular vesicles LC-MS/MS

Project description:In this study we have compared the proteomic profile of extracellular vesicles (EVs) prepared from primary, human NK cells or the human NK cell lines NK-92 and KHYG-1 cultured for 48hrs in serum-free conditions. EVs were harvested from cells either under resting conditions (culture in IL-15) or upon activation (combination of IL-12, IL-15, and IL-18). In addition, primary NK cells were activated in the presence of anti-CD16-coated beads, and EVs harvested after 48hrs. The aim was to compare their ability to target and kill a variety of tumor cell line-derived spheroids

2022-10-14 | PXD027284 | Pride

Gene expression profiles of human Natural Killer Cells, unstimulated and stimulated with IPH6501, a tetraspecific NK cell engager (NKCE).

Project description:The impact of IPH6501 treatment on the transcriptome of blood NK cells was dissequed using scRNA seq analysis. Unsupervised analysis of human blood NK cells revealed significant transcriptomic changes across NK1, NK2, and NK3 cell subsets following in vitro stimulation by CD20-NKCE-IL2v, indicating that treatment affect all NK cell subsets. Stimulation with the CD20-NKCE-IL2v led to the emergence of another NK cell cluster characterized by a signature resembling cytokine-induced memory-like (CIML) NK cells similar to that found in NK cells activated by IL-2/IL-15/IL-12/IL-18. This population was observed at both 4- and 24-hours post-stimulation.

2024-08-07 | GSE273867 | GEO

EZH2 identifies the precursors for trained immunity of human natural killer cells

Project description:Human NK cells were treated with IL-12/15/18 to induce trained immunity. scRNA-seq and TotalSeqTM were performed to map the development pathway of trained NK cells.

2020-09-23 | GSE158349 | 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