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Tumor-selective Blockade of CD47 Signaling with CD47 Antibody for Enhanced Antitumor Activity in Malignant Meningioma

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机构: [1]Southern Medical University, Guangzhou, Guangdong, China. [2]Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [3]College of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
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Patients with WHO grade III meningioma have a poor prognosis with a median survival of less than two years and a high risk of recurrence. However, traditional treatment options have failed to improve prognosis. Therefore, development of novel immunotherapy targets is urgently needed. CD47 acting as a "don't eat me" signal to macrophages can trigger tumor immune escape. However, the role of CD47 in malignant meningioma is not well understood.We collected 190 clinical meningioma samples and detected the expression of CD47 and immune infiltration in WHO grade I-III by immunohistochemistry, western blot, qPCR. We also ex- amined the functional effects of anti-CD47 on cell proliferation, migration and invasion, macrophage- mediated phagocytosis and tumorigenicity both in vitro and in vivo.We found that the expression of CD47 was increased in malignant meningioma along with a decreased number of T cells and an increase in CD68+ macrophages. Blocking CD47 with anti-CD47 antibody (B6H12) suppressed tumor cell growth, motility and promoted macrophage-mediated phagocytosis in IOMM-Lee cells in vitro. In vivo experiments showed that anti-CD47 antibody (B6H12 or MIAP301) significantly inhibited the tumor growth and this effect was partly blocked by the depletion of macrophages. Finally, p-ERK and EGFR showed higher expression in malignant meningioma with high expression of CD47, which was verified by western blot.Our results demonstrated that CD47 maybe involved in the meningioma progression andprognosis and offered a novel therapeutic option by targeting CD47 in malignant meningioma.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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出版当年[2022]版
大类 | 2 区 医学
小类 | 2 区 神经科学 2 区 药学
最新[2025]版
大类 | 3 区 医学
小类 | 2 区 药学 3 区 神经科学
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第一作者机构: [1]Southern Medical University, Guangzhou, Guangdong, China.
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