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The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ
BACKGROUND: Metabolic reprogramming occurs in the tumor microenvironment and influences the survival and function of tumor and immune cells. Interferon-γ (IFN-γ) produced by T cells up-regulates PD-L1 expression in tumors. However, reports regarding the relationship between nutrient metabolism and t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203092/ https://www.ncbi.nlm.nih.gov/pubmed/30425515 http://dx.doi.org/10.2147/OTT.S180505 |
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author | Wang, Liping Yang, Xuecheng Li, Dan Liang, Zhijuan Chen, Yuanbin Ma, Guofeng Wang, Yonghua Li, Yongxin Liang, Ye Niu, Haitao |
author_facet | Wang, Liping Yang, Xuecheng Li, Dan Liang, Zhijuan Chen, Yuanbin Ma, Guofeng Wang, Yonghua Li, Yongxin Liang, Ye Niu, Haitao |
author_sort | Wang, Liping |
collection | PubMed |
description | BACKGROUND: Metabolic reprogramming occurs in the tumor microenvironment and influences the survival and function of tumor and immune cells. Interferon-γ (IFN-γ) produced by T cells up-regulates PD-L1 expression in tumors. However, reports regarding the relationship between nutrient metabolism and the up-regulation of PD-L1 expression are lacking. MATERIALS AND METHODS: In this paper, we analyzed the metabolic changes in T cells and bladder cancer cells in a simulated tumor microenvironment to provide evidence regarding their relevance to PD-L1 up-regulation. RESULTS: The glutaminolysis was increased in both activated T cells and glucose-deprived T cells. IFN-γ production by T cells was decreased in a glucose-free medium and severely decreased when cells were simultaneously deprived of glutamine. Furthermore, the glutaminolysis of the bladder cancer cells under glucose deprivation exhibited a compensatory elevation. The glucose concentration of T cells co-cultured with bladder cancer cells was decreased and T cell proliferation was reduced, but IFN-γ production and glutaminolysis were increased. However, in bladder cancer cells, the elevation in glutaminolysis under co-culture conditions did not compensate for glucose deprivation because the glucose concentration in the culture medium did not significantly differ between the cultures with and without T cells. Our data also show that inhibiting glutamine metabolism in bladder cancer cells could reduce the elevation in PD-L1 expression induced by IFN-γ. CONCLUSION: In a simulated tumor microenvironment, elevated glutaminolysis may play an essential role in IFN-γ production by T cells, ultimately improving the high PD-L1 expression, and also directly contributing to producing more PD-L1 in bladder cancer cells. |
format | Online Article Text |
id | pubmed-6203092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62030922018-11-13 The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ Wang, Liping Yang, Xuecheng Li, Dan Liang, Zhijuan Chen, Yuanbin Ma, Guofeng Wang, Yonghua Li, Yongxin Liang, Ye Niu, Haitao Onco Targets Ther Original Research BACKGROUND: Metabolic reprogramming occurs in the tumor microenvironment and influences the survival and function of tumor and immune cells. Interferon-γ (IFN-γ) produced by T cells up-regulates PD-L1 expression in tumors. However, reports regarding the relationship between nutrient metabolism and the up-regulation of PD-L1 expression are lacking. MATERIALS AND METHODS: In this paper, we analyzed the metabolic changes in T cells and bladder cancer cells in a simulated tumor microenvironment to provide evidence regarding their relevance to PD-L1 up-regulation. RESULTS: The glutaminolysis was increased in both activated T cells and glucose-deprived T cells. IFN-γ production by T cells was decreased in a glucose-free medium and severely decreased when cells were simultaneously deprived of glutamine. Furthermore, the glutaminolysis of the bladder cancer cells under glucose deprivation exhibited a compensatory elevation. The glucose concentration of T cells co-cultured with bladder cancer cells was decreased and T cell proliferation was reduced, but IFN-γ production and glutaminolysis were increased. However, in bladder cancer cells, the elevation in glutaminolysis under co-culture conditions did not compensate for glucose deprivation because the glucose concentration in the culture medium did not significantly differ between the cultures with and without T cells. Our data also show that inhibiting glutamine metabolism in bladder cancer cells could reduce the elevation in PD-L1 expression induced by IFN-γ. CONCLUSION: In a simulated tumor microenvironment, elevated glutaminolysis may play an essential role in IFN-γ production by T cells, ultimately improving the high PD-L1 expression, and also directly contributing to producing more PD-L1 in bladder cancer cells. Dove Medical Press 2018-10-18 /pmc/articles/PMC6203092/ /pubmed/30425515 http://dx.doi.org/10.2147/OTT.S180505 Text en © 2018 Wang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Wang, Liping Yang, Xuecheng Li, Dan Liang, Zhijuan Chen, Yuanbin Ma, Guofeng Wang, Yonghua Li, Yongxin Liang, Ye Niu, Haitao The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title | The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title_full | The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title_fullStr | The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title_full_unstemmed | The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title_short | The elevated glutaminolysis of bladder cancer and T cells in a simulated tumor microenvironment contributes to the up-regulation of PD-L1 expression by interferon-γ |
title_sort | elevated glutaminolysis of bladder cancer and t cells in a simulated tumor microenvironment contributes to the up-regulation of pd-l1 expression by interferon-γ |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203092/ https://www.ncbi.nlm.nih.gov/pubmed/30425515 http://dx.doi.org/10.2147/OTT.S180505 |
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