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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783474737380327424 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6885434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wanghelin cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT yanzhuohong cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT haojianqing cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT yangbin cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT wangjinghui cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT yiling cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT wangxiaojue cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT lishuping cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT zhanghongtao cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng AT zhangshucai cd137ligandfeedbackupregulatespdl1expressiononlungcancerviatcellproductionofifng |