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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175862 | GEO | 2021/06/02

REPOSITORIES: GEO

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

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. Here we report the RNA sequencing for the CHMP2A KO glioblastoma stem cells CW468 and 387

2021-06-02 | GSE175863 | GEO

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

Mechanisms of Cancer Resistance to Immunogenic Cytotoxicity

Project description:The majority of cancer patients do not respond to immunotherapy. In order to systematically discover pathways promoting cancer cell resistance to effector immune cells, we generated immunity-resistant Head and Neck Squamous Cell Carcinoma cell lines. We utilized RNA-Seq to determine what are the genes and pathways that are significantly altered when cancer cells become resistant to effectors.

2018-12-25 | GSE100828 | GEO

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>.

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CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-02 | GSE175864 | GEO

Gene expression profiles of head and neck squamous cell carcinoma

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Gene expression analysis of head and neck squamous cell carcinoma cell lines and a control normal oral epithelial cell line

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Human Natural Killer Cell activation by mycobacteria

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