The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy
Abstract Background PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenv...
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doaj-390881c9a7f840b196743b49e6f958b12020-11-25T01:39:01ZengBMCJournal of Neuroinflammation1742-20942018-10-0115111310.1186/s12974-018-1330-2The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapyJiawen Qian0Chen Wang1Bo Wang2Jiao Yang3Yuedi Wang4Feifei Luo5Junying Xu6Chujun Zhao7Ronghua Liu8Yiwei Chu9Department of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityJiangsu Key Lab of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of SciencesDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityBiotherapy Research Center, Fudan UniversityDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityNorthfield Mount Hermon SchoolDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityDepartment of Immunology, School of Basic Medical Sciences, and Institute of Biomedical Sciences, Fudan UniversityAbstract Background PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies. Methods The distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model. The expression of PD-L1 in immune cell populations was detected by flow cytometry. Data excavated from TCGA LGG/GBM datasets and the Ivy Glioblastoma Atlas Project was used for in silico analysis of the correlation among genes and survival. Results The distribution of tumor-infiltrating T cells and PD-L1 expression, which parallels in murine orthotopic glioma model and human glioma microdissections, was interrelated. The IFN-γ level was positively correlated with PD-L1 expression in murine glioma. Further, IFN-γ induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN-γ-induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN-γ level. By combining the relative expression of the listed IFN-γ-induced genes, IFN-γ score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies. Conclusion Our study identified the distribution of tumor-infiltrating T cells and PD-L1 expression in murine glioma model and human glioma samples. And we found that IFN-γ is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN-γ score aggregated from the expressions of the listed IFN-γ-induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy.http://link.springer.com/article/10.1186/s12974-018-1330-2PD-L1Immune checkpointIFN-γGliomaImmune evasion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiawen Qian Chen Wang Bo Wang Jiao Yang Yuedi Wang Feifei Luo Junying Xu Chujun Zhao Ronghua Liu Yiwei Chu |
spellingShingle |
Jiawen Qian Chen Wang Bo Wang Jiao Yang Yuedi Wang Feifei Luo Junying Xu Chujun Zhao Ronghua Liu Yiwei Chu The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy Journal of Neuroinflammation PD-L1 Immune checkpoint IFN-γ Glioma Immune evasion |
author_facet |
Jiawen Qian Chen Wang Bo Wang Jiao Yang Yuedi Wang Feifei Luo Junying Xu Chujun Zhao Ronghua Liu Yiwei Chu |
author_sort |
Jiawen Qian |
title |
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy |
title_short |
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy |
title_full |
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy |
title_fullStr |
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy |
title_full_unstemmed |
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy |
title_sort |
ifn-γ/pd-l1 axis between t cells and tumor microenvironment: hints for glioma anti-pd-1/pd-l1 therapy |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2018-10-01 |
description |
Abstract Background PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies. Methods The distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model. The expression of PD-L1 in immune cell populations was detected by flow cytometry. Data excavated from TCGA LGG/GBM datasets and the Ivy Glioblastoma Atlas Project was used for in silico analysis of the correlation among genes and survival. Results The distribution of tumor-infiltrating T cells and PD-L1 expression, which parallels in murine orthotopic glioma model and human glioma microdissections, was interrelated. The IFN-γ level was positively correlated with PD-L1 expression in murine glioma. Further, IFN-γ induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN-γ-induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN-γ level. By combining the relative expression of the listed IFN-γ-induced genes, IFN-γ score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies. Conclusion Our study identified the distribution of tumor-infiltrating T cells and PD-L1 expression in murine glioma model and human glioma samples. And we found that IFN-γ is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN-γ score aggregated from the expressions of the listed IFN-γ-induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy. |
topic |
PD-L1 Immune checkpoint IFN-γ Glioma Immune evasion |
url |
http://link.springer.com/article/10.1186/s12974-018-1330-2 |
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