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Characterization of Natural Killer Cell Sensitivity of Circulating Tumor Cells in Non-small Cell Lung Cancer using Bulk RNA-sequencing

ABSTRACT: To investigate whether circulating tumor cells exhibit NK sensitive gene expression profiles, we performed bulk RNA-sequencing on NK sensitive and NK resisitant cell lines, including two in-house derived CTC lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211830 | GEO | 2023/01/15

REPOSITORIES: GEO

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Resting natural killer cell homeostasis relies on tryptophan/NAD+ metabolism and HIF-1α

Project description:Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining in situ metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1a as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+) levels. The HIF-1a/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steadystate conditions. In contrast, in activated NK cells under hypoxia, HIF-1a is required for glycolysis, and forced HIF-1a expression boosts glycolysis and NK cell performance in vitro and in vivo. Our data highlight two distinct pathways by which HIF-1a interferes with NK cell metabolism. While HIF-1a-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1a-dependent tryptophan/NAD+ metabolism. Linked cross omic data sets:RNA-seq data associated with this study are available in ArrayExpress (BioStudies): accession <a href='https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-12082' rel='noopener noreferrer' target='_blank'>E-MTAB-12082</a>.

2023-06-01 | MTBLS6863 | MetaboLights

Transcription profiling by array of human natural killer cell lines, normal donors and clinical samples of natural killer cell neoplasms to detect tumor-specific genes

Project description:Comprehensive gene expression profiles of seven NK cell lines and eleven clinical samples of NK cell neoplasm were analyzed to detect tumor-specific genes. The gene expression profiles of NK cells from normal donor were analyzed as control samples.

2011-06-11 | E-MEXP-2996 | biostudies-arrayexpress

Transcription profiling of natural-killer (NK) cell lymphoma to determine the disease molecular signature.

Project description:NK-cell lymphoma shares strikingly similar molecular features with a distinct subset of gamma-delta T-cell lymphoma. Gene expression profiling of NK-cell lymphoma patient samples was performed to investigate whether molecular signatures can be used to identify entities of peripheral T-cell lymphoma (PTCL) with NK-cell-like features. Gene expression profiling was performed on NK-cell maligancies to examine extranodal NK/T-cell lymphoma (ENKTL) and aggressive NK-cell leukemia (ANKL) and well-characterized cell lines of NK- and T-cell lineages to define molecular classifiers that can distinguish ENKTL from other lymphomas.

2010-03-18 | E-GEOD-19067 | biostudies-arrayexpress

Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity

Project description:STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing Stat1-Y701F. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity. As expected Stat1-Y701F mice displayed impaired NK cell maturation comparable to Stat1-/- animals. In contrast Stat1-Y701F NK cells exerted a significantly enhanced cytotoxicity in vitro and in vivo suggesting a so-far unknown cytoplasmic function. Using immunofluorescence technology we uncovered the recruitment of STAT1 to the immunological synapse during NK cell killing. A Stat1ind mouse expressing FLAG-tagged STAT1α was used to study the STAT1α interactome in NK cells. Mass spectrometry revealed that STAT1 directly binds proteins involved in cell junction formation and proteins associated to membrane or membrane-bound vesicles. We propose a novel function for STAT1 in the immunological synapse of NK cells regulating tumor surveillance and cytotoxicity.

2016-10-07 | PXD002206 | Pride

CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity [CRISPR]

Project description:We report the application of a two-cell -type whole genome KO CRISPR screen to find new moecular targets that increase the sensitivity or resistance to NK cells cytotoxixity in glioblastoma stem cells and head and neck squamous cells carcinoma cells.

2021-06-02 | GSE175862 | GEO

miRNA expression profiling of NKTCL (Natural Killer/T-Cell Lymphoma) samples

Project description:We performed a comprehensive genome-wide miRNA expression profiling (MEP) of extranodal nasal-type Natural Killer/T-cell lymphoma (NKTL) using formalin fixed paraffin-embedded tissue (FFPE) (n=30) and NK cell lines (n=6) in comparison with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Total RNA, including miRNA, were extracted using Ambion Recoverall Kit and profiled using Agilent human miRNA V2.

2011-11-23 | E-GEOD-31377 | biostudies-arrayexpress

Human Natural Killer Cell activation by mycobacteria

Project description:Purified NK cells were co-cultured with M. bovis BCG or M. tuberculosis H37Rv (1:1) in the presence of IL-2 (100U/ml) or IL-12 (10pg/ml) for 24h before trizol extraction. We used microarrays to detail the global gene expression underlying NK cell activation by mycobacteria. NK cell were isolated from the blood of 6 independent donors and activated with different mycobacteria and cytokines in order to study their transcriptional profiles according to mycobacterial virulence.

2011-07-26 | E-GEOD-30950 | biostudies-arrayexpress

MicroRNA-15/16 Antagonizes c-Myb to Control Natural Killer Cell Maturation (c-Myb overexpression)

Project description:NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program. KY-1 and KY-2 cell lines overexpressing c-Myb

2015-09-03 | E-GEOD-58268 | biostudies-arrayexpress

Natural killer receptor-positive innate lymphoid cells

Project description:The following lymphocytes were sorted from the lamin propria of the small intestine of EomesGfg/+ RORgtCreTGg Rosa26Yfp/+ by using the markers Lineage- CD45+ Nkp46+ NK1.1+ : 1.convential NK cells (Eomes GFP+ RORgt YFP-) 2. ILC1 (Eomes GFP- RORgt YFP-) 3. exRORgt ILC3 (Eomes GFP- RORgt YFP+). Conventional NK cells from the bone marrow (cNK BM) were sorted from Eomes Gfp/+ mice with the markers Lineage- CD45+ NK1.1+ Eomes GFP+.

2014-04-15 | E-MTAB-2428 | biostudies-arrayexpress

CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity [RNA-seq]

2021-06-02 | GSE175863 | GEO

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