期刊
JOURNAL OF NEUROINFLAMMATION
卷 15, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12974-018-1330-2
关键词
PD-L1; Immune checkpoint; IFN-; Glioma; Immune evasion
资金
- National Natural Science Foundation of China [31570892, 31770992, 81730045, 91527305]
- Science and Technology Commission of Shanghai Municipality [15JC1401200]
BackgroundPD-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.MethodsThe 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.ResultsThe 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- level was positively correlated with PD-L1 expression in murine glioma. Further, IFN- induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN--induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN- level. By combining the relative expression of the listed IFN--induced genes, IFN- score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies.ConclusionOur 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- is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN- score aggregated from the expressions of the listed IFN--induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy.
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