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CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175864 | GEO | 2021/06/02

REPOSITORIES: GEO

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CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity.

Project description:Natural killer (NK) cells are known to mediate killing of various cancer types, but tumor cells can develop resistance mechanisms to escape NK cell-mediated killing. Here, we use a "two cell type" whole genome CRISPR-Cas9 screening system to discover key regulators of tumor sensitivity and resistance to NK cell-mediated cytotoxicity in human glioblastoma stem cells (GSC). We identify CHMP2A as a regulator of GSC resistance to NK cell-mediated cytotoxicity and we confirm these findings in a head and neck squamous cells carcinoma (HNSCC) model. We show that deletion of CHMP2A activates NF-κB in tumor cells to mediate increased chemokine secretion that promotes NK cell migration towards tumor cells. In the HNSCC model we demonstrate that CHMP2A mediates tumor resistance to NK cells via secretion of extracellular vesicles (EVs) that express MICA/B and TRAIL. These secreted ligands induce apoptosis of NK cells to inhibit their antitumor activity. To confirm these in vitro studies, we demonstrate that deletion of CHMP2A in CAL27 HNSCC cells leads to increased NK cell-mediated killing in a xenograft immunodeficient mouse model. These findings illustrate a mechanism of tumor immune escape through EVs secretion and identify inhibition of CHMP2A and related targets as opportunities to improve NK cell-mediated immunotherapy.

| S-EPMC8990014 | biostudies-literature

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

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

2021-06-02 | GSE175863 | GEO

Runx3 Regulates Interleukin-15-Dependent Natural Killer Cell Activation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-22 | E-GEOD-52625 | biostudies-arrayexpress

CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

Project description:CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

| PRJNA734153 | ENA

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

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

| PRJNA734155 | ENA

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

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

| PRJNA734156 | ENA

Runx3 Regulates Interleukin-15-Dependent Natural Killer Cell Activation

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

2014-01-22 | GSE52625 | GEO

Natural killer cells suppress T cell tumor immune evasion

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

2019-07-16 | GSE134265 | GEO

Themis2 regulates the differentiation and function of memory natural killer cells

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

2023-09-26 | GSE227139 | GEO

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