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作者

Xing-Chen,Ding Liang-Liang,Wang Xue-Dong,Zhang Jun-Long,Xu Pei-Feng,Li Hua,Liang Xian-Bin,Zhang Li,Xie Zi-Han,Zhou Jia,Yang Ralph R,Weichselbaum Jin-Ming,Yu Man,Hu

作者单位

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Ji Yan Road, Jinan, Shandong, China. sdyujinming@16 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Ji Yan Road, Jinan, Shandong, China. ' Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, 60637, USA. rrw@radonc.uchicago.edu. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Ji Yan Road, Jinan, Shandong, China. human5770@16 ' Department of General Surgery, Shenzhen University General Hospital & Carson International Cancer Research Centre, Shenzhen, China. Department of Pathology, The 960Th Hospital of PLA, Jinan, Shandong, China. Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, 60637, USA. Department of Oncology, Weifang Medical University, Weifang, Shandong, China. com. Department of Pathology, Liaocheng Hospital of China, Liaocheng, Shandong, China.

刊名

Journal of hematology & oncology [electronic resource]

年份

2021

卷号

Vol.14 No.1

页码

92

关键词

Glioma HIF-1 α Hypoxia Immunotherapy PD-L1

摘要

Hypoxia inducible factor-1α up-regulates the expression of programmed death ligand-1 in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD...更多

Hypoxia inducible factor-1α up-regulates the expression of programmed death ligand-1 in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell and CD8 + T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.收起

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