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Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1

INTRODUCTION: The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. Thi...

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Autores principales: Han, Fengfeng, Guo, Shuwei, Huang, Chao, Cui, Linjing, Zhao, Yuanyuan, Ma, Jie, Zhu, Miaolin, Chen, Zhihong, Wang, Mei, Shen, Bo, Zhu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808309/
https://www.ncbi.nlm.nih.gov/pubmed/35125940
http://dx.doi.org/10.5114/ceji.2021.111753
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author Han, Fengfeng
Guo, Shuwei
Huang, Chao
Cui, Linjing
Zhao, Yuanyuan
Ma, Jie
Zhu, Miaolin
Chen, Zhihong
Wang, Mei
Shen, Bo
Zhu, Wei
author_facet Han, Fengfeng
Guo, Shuwei
Huang, Chao
Cui, Linjing
Zhao, Yuanyuan
Ma, Jie
Zhu, Miaolin
Chen, Zhihong
Wang, Mei
Shen, Bo
Zhu, Wei
author_sort Han, Fengfeng
collection PubMed
description INTRODUCTION: The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. This study aimed to determine whether GCMSCs are involved in the inhibition of NK cell immune function and explore its underlying mechanism. MATERIAL AND METHODS: CD107a and perforin expression of GCMSCs conditioned medium (GCMSCs-CM)-primed NK cells were detected by flow cytometry. To determine NK cell cytotoxicity, the CytoTox96 Non-Radioactive Cytotoxicity Assay kit was used. Glucose uptake and lactate production assay were performed to evaluate the metabolism state of NK cells treated with GCMSCs-CM. The expression of FBP1 in NK cells was analysed by immunoblotting. RESULTS: GCMSCs inhibited the degranulation capacity, perforin production and cytotoxicity of NK cells. GCMSCs-CM restrained NK cell glucose uptake and lactate production, thus weakening their glycolytic metabolism. FBP1 expression of NK cells was upregulated in the presence of GCMSCs-CM. Using FBP1 inhibitor could reverse the dysfunctional state of NK cells. CONCLUSIONS: This study indicated that GCMSCs could exert immunosuppressive effects on NK cells by up-regulating FBP1 expression, opening up new avenues for NK cell-based GC immunotherapy.
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spelling pubmed-88083092022-02-04 Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1 Han, Fengfeng Guo, Shuwei Huang, Chao Cui, Linjing Zhao, Yuanyuan Ma, Jie Zhu, Miaolin Chen, Zhihong Wang, Mei Shen, Bo Zhu, Wei Cent Eur J Immunol Experimental Immunology INTRODUCTION: The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. This study aimed to determine whether GCMSCs are involved in the inhibition of NK cell immune function and explore its underlying mechanism. MATERIAL AND METHODS: CD107a and perforin expression of GCMSCs conditioned medium (GCMSCs-CM)-primed NK cells were detected by flow cytometry. To determine NK cell cytotoxicity, the CytoTox96 Non-Radioactive Cytotoxicity Assay kit was used. Glucose uptake and lactate production assay were performed to evaluate the metabolism state of NK cells treated with GCMSCs-CM. The expression of FBP1 in NK cells was analysed by immunoblotting. RESULTS: GCMSCs inhibited the degranulation capacity, perforin production and cytotoxicity of NK cells. GCMSCs-CM restrained NK cell glucose uptake and lactate production, thus weakening their glycolytic metabolism. FBP1 expression of NK cells was upregulated in the presence of GCMSCs-CM. Using FBP1 inhibitor could reverse the dysfunctional state of NK cells. CONCLUSIONS: This study indicated that GCMSCs could exert immunosuppressive effects on NK cells by up-regulating FBP1 expression, opening up new avenues for NK cell-based GC immunotherapy. Termedia Publishing House 2021-12-23 2021 /pmc/articles/PMC8808309/ /pubmed/35125940 http://dx.doi.org/10.5114/ceji.2021.111753 Text en Copyright © 2021 Termedia https://creativecommons.org/licenses/by-nc-sa/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/ (https://creativecommons.org/licenses/by-nc-sa/4.0/) )
spellingShingle Experimental Immunology
Han, Fengfeng
Guo, Shuwei
Huang, Chao
Cui, Linjing
Zhao, Yuanyuan
Ma, Jie
Zhu, Miaolin
Chen, Zhihong
Wang, Mei
Shen, Bo
Zhu, Wei
Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title_full Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title_fullStr Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title_full_unstemmed Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title_short Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1
title_sort gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating fbp1
topic Experimental Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808309/
https://www.ncbi.nlm.nih.gov/pubmed/35125940
http://dx.doi.org/10.5114/ceji.2021.111753
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