The relationship between expression of PD-L1 and HIF-1[alpha] in glioma cells under hypoxia.

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From: Journal of Hematology & Oncology(Vol. 14, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Article
Length: 1,946 words
Lexile Measure: 1420L

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Abstract :

Hypoxia inducible factor-1[alpha] (HIF-1[alpha]) up-regulates the expression of programmed death ligand-1 (PD-L1) 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-1[alpha] and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1[alpha] 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-1[alpha] knock-down or HIF-1[alpha] inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1[alpha] to PD-L1 proximal promoter region, providing evidence that HIF-1[alpha] up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1[alpha] 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 (DC) and CD8.sup.+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1[alpha] in glioma, and provide an alternative strategy, inhibiting HIF-1[alpha], as combination therapies with immunotherapies to advance glioma treatment. Keywords: PD-L1, HIF-1 [alpha], Glioma, Hypoxia, Immunotherapy

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Gale Document Number: GALE|A665426101