CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ

BACKGROUND: The expression of PD‐L1 and its regulation in tumors remains unclear. The importance of IFN‐γ in upregulating the PD‐L1 expression in various tumors, and the effects of other essential cytokines in the tumor microenvironment (TME), need to be further elucidated. METHODS: Constitutive exp...

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Autores principales: Wang, Helin, Yan, Zhuohong, Hao, Jianqing, Yang, Bin, Wang, Jinghui, Yi, Ling, Wang, Xiaojue, Li, Shuping, Zhang, Hongtao, Zhang, Shucai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885434/
https://www.ncbi.nlm.nih.gov/pubmed/31625289
http://dx.doi.org/10.1111/1759-7714.13207
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author Wang, Helin
Yan, Zhuohong
Hao, Jianqing
Yang, Bin
Wang, Jinghui
Yi, Ling
Wang, Xiaojue
Li, Shuping
Zhang, Hongtao
Zhang, Shucai
author_facet Wang, Helin
Yan, Zhuohong
Hao, Jianqing
Yang, Bin
Wang, Jinghui
Yi, Ling
Wang, Xiaojue
Li, Shuping
Zhang, Hongtao
Zhang, Shucai
author_sort Wang, Helin
collection PubMed
description BACKGROUND: The expression of PD‐L1 and its regulation in tumors remains unclear. The importance of IFN‐γ in upregulating the PD‐L1 expression in various tumors, and the effects of other essential cytokines in the tumor microenvironment (TME), need to be further elucidated. METHODS: Constitutive expression of PD‐L1 and CD137L in all 13 lung cancer cell lines were tested by flow cytometry. CD137L mRNA of lung cancer cell lines was detected by RT‐PCR. PD‐L1 expression rates following stimulation with these cytokines (IFN‐γ, TNFα and IL2) were measured. After coculture of cells expressing CD137L (lung cancer cells or 293FT cells transfected with CD137L plasmid) with T cells, the PDL1 expression of lung cancer cells and IFN‐γ in supernatant was detected. RESULTS: Our data revealed that adenocarcinoma and squamous cell carcinoma cells had the highest positive expression rate. IFN‐γ was the core‐inducing factor for enhancing the PD‐L1 expression. CD137L was also widely expressed in the lung cancer cell lines at the mRNA level, whereas its expression was generally low at the protein level. However, the low expression of CD137L protein was still enough to induce T cells to produce IFN‐γ, which subsequently increased the PD‐L1 expression by lung cancer cells. The CD137 signal induces IFN‐γ secretion by T cells, which stimulates high‐level of PD‐L1 expression in cancer cells; this negative immune regulation may represent a mechanism of immune escape regulation. CONCLUSIONS: CD137L mRNA was widely expressed in lung cancer cell lines whereas levels of protein expression were generally low. The low level of CD137L protein was still enough to induce T cells to produce IFN‐γ that subsequently increased PD‐L1 expression. The CD137L‐induced negative immune regulation may represent a mechanism of immune escape.
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spelling pubmed-68854342019-12-09 CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ Wang, Helin Yan, Zhuohong Hao, Jianqing Yang, Bin Wang, Jinghui Yi, Ling Wang, Xiaojue Li, Shuping Zhang, Hongtao Zhang, Shucai Thorac Cancer Original Articles BACKGROUND: The expression of PD‐L1 and its regulation in tumors remains unclear. The importance of IFN‐γ in upregulating the PD‐L1 expression in various tumors, and the effects of other essential cytokines in the tumor microenvironment (TME), need to be further elucidated. METHODS: Constitutive expression of PD‐L1 and CD137L in all 13 lung cancer cell lines were tested by flow cytometry. CD137L mRNA of lung cancer cell lines was detected by RT‐PCR. PD‐L1 expression rates following stimulation with these cytokines (IFN‐γ, TNFα and IL2) were measured. After coculture of cells expressing CD137L (lung cancer cells or 293FT cells transfected with CD137L plasmid) with T cells, the PDL1 expression of lung cancer cells and IFN‐γ in supernatant was detected. RESULTS: Our data revealed that adenocarcinoma and squamous cell carcinoma cells had the highest positive expression rate. IFN‐γ was the core‐inducing factor for enhancing the PD‐L1 expression. CD137L was also widely expressed in the lung cancer cell lines at the mRNA level, whereas its expression was generally low at the protein level. However, the low expression of CD137L protein was still enough to induce T cells to produce IFN‐γ, which subsequently increased the PD‐L1 expression by lung cancer cells. The CD137 signal induces IFN‐γ secretion by T cells, which stimulates high‐level of PD‐L1 expression in cancer cells; this negative immune regulation may represent a mechanism of immune escape regulation. CONCLUSIONS: CD137L mRNA was widely expressed in lung cancer cell lines whereas levels of protein expression were generally low. The low level of CD137L protein was still enough to induce T cells to produce IFN‐γ that subsequently increased PD‐L1 expression. The CD137L‐induced negative immune regulation may represent a mechanism of immune escape. John Wiley & Sons Australia, Ltd 2019-10-17 2019-12 /pmc/articles/PMC6885434/ /pubmed/31625289 http://dx.doi.org/10.1111/1759-7714.13207 Text en © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wang, Helin
Yan, Zhuohong
Hao, Jianqing
Yang, Bin
Wang, Jinghui
Yi, Ling
Wang, Xiaojue
Li, Shuping
Zhang, Hongtao
Zhang, Shucai
CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title_full CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title_fullStr CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title_full_unstemmed CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title_short CD137 ligand feedback upregulates PD‐L1 expression on lung cancer via T cell production of IFN‐γ
title_sort cd137 ligand feedback upregulates pd‐l1 expression on lung cancer via t cell production of ifn‐γ
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885434/
https://www.ncbi.nlm.nih.gov/pubmed/31625289
http://dx.doi.org/10.1111/1759-7714.13207
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