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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE175863 | GEO | 2021/06/02

REPOSITORIES: GEO

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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.

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.

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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

Abernathy2016 - glioblastoma treatment

Project description:The paper describes a model of glioblastoma. Created by COPASI 4.25 (Build 207) This model is described in the article: Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations Kristen Abernathy and Jeremy Burke BMC Computational and Mathematical Methods in Medicine Volume 2016, Article ID 1239861, 11 pages Abstract: Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

2024-09-02 | BIOMD0000000757 | BioModels

Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition.

Project description:Natural killer (NK) cells can recognize and kill tumor cells lacking "self" markers, such as class I MHC, but the basis for this recognition is not completely understood. NKR-P1 receptors are members of the C-type lectin-related NK receptor superfamily that are conserved from rodents to humans. Identification of Clr ligands for the NKR-P1 receptors has facilitated functional analysis of MHC-independent target cell recognition by NK cells. One receptor-ligand pair, NKR-P1B:Clr-b, can mediate "missing-self" recognition of tumor and infected cells, but the role of this axis in sensing stressed cells remains unknown. Here, we show that Clr-b is rapidly downregulated in cells undergoing genotoxic and cellular stress at the level of both RNA and surface protein. Stress-mediated loss of Clr-b on leukemia cells enhanced cytotoxicity mediated by NKR-P1B(+) NK cells. Notably, Clr-b downregulation was coordinated functionally with stress-mediated upregulation of NKG2D ligands (but not class I MHC). Our findings highlight a unique role for the MHC-independent NKR-P1B:Clr-b missing-self axis in recognition of stressed cells, and provide evidence of two independent levels of Clr-b regulation in stressed cells.

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Project description:Glioblastoma stem cells

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CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity

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

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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.

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Human expression data from Glioblastoma cell malignancy and drug sensitivity are affected by the cell of origin.

Project description:The cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy. We have investigated the role of cell of origin in glioblastoma by inducing glioblastomas of defined cell of origin using PDGFB in the brains of adult mice. Gene expression was analysed from cultured mouse glioblastoma cells and a mouse cell origin gene signature was extracted that we used in a cluster analysis on gene expression data from patient-derived glioblastoma cell lines.

2017-01-23 | GSE91392 | GEO

Mouse expression data from Glioblastoma cell malignancy and drug sensitivity are affected by the cell of origin.

2017-01-23 | GSE91391 | GEO