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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Research Article

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

Author(s): Xiaotong Liu, Huarong Zhang, Chaohu Wang, Zhiyong Li, Qianchao Zhu, Yiwen Feng, Jun Fan, Songtao Qi*, Zhiyong Wu* and Yi Liu*

Volume 21, Issue 10, 2023

Published on: 27 June, 2023

Page: [2159 - 2173] Pages: 15

DOI: 10.2174/1570159X21666230511123157

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Abstract

Background: 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.

Methods: 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 examined the functional effects of anti-CD47 on cell proliferation, migration and invasion, macrophagemediated phagocytosis and tumorigenicity both in vitro and in vivo.

Results: 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.

Conclusion: Our results demonstrated that CD47 maybe involved in the meningioma progression and prognosis and offered a novel therapeutic option by targeting CD47 in malignant meningioma.

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