PDF(Pubmed)
Abstract：
Cluster of differentiation 47 (CD47) is a transmembrane protein that is widely and moderately expressed on the surface of various cells and can have an essential role in mediating cell proliferation, migration, phagocytosis, apoptosis, immune homeostasis and other related responses by binding to its ligands, integrins, thrombospondin-1 and signal regulatory protein α. The poor prognosis of cancer patients is closely associated with high expression of CD47 in glioblastoma, ovarian cancer, breast cancer, bladder cancer, colon cancer and hepatocellular carcinoma. Upregulation of CD47 expression facilitates the growth of numerous types of tumor cells, while downregulation of its expression promotes phagocytosis of tumor cells by macrophages, thereby limiting tumor growth. In addition, blocking CD47 activates the cyclic GMP-AMP (cGAMP) synthase/cGAMP/interferon gene stimulating factor signaling pathway and initiates an adaptive immune response that kills tumor cells. The present review describes the structure, function and interactions of CD47 with its ligands, as well as its regulation of phagocytosis and tumor cell fate. It summarizes the therapeutics, mechanisms of action, research advances and challenges of targeting CD47. In addition, this paper provides an overview of the latest therapeutic options for targeting CD47, such as chimeric antigen receptor (CAR) T-cells, CAR macrophages and nanotechnology-based delivery systems, which are essential for future clinical research on targeting CD47.
摘要：
分化簇47（CD47）是一种跨膜蛋白，在各种细胞表面广泛而中等表达，在介导细胞增殖中起重要作用，迁移,吞噬作用,凋亡，免疫稳态和其他相关的反应，通过结合其配体，整合素,血小板反应蛋白-1和信号调节蛋白α。CD47在胶质母细胞瘤中的高表达与肿瘤患者预后差密切相关,卵巢癌,乳腺癌,膀胱癌,结肠癌和肝细胞癌。CD47表达上调促进多种类型肿瘤细胞的生长，而其表达下调促进巨噬细胞吞噬肿瘤细胞，从而限制肿瘤的生长。此外,阻断CD47激活环GMP-AMP（cGAMP）合酶/cGAMP/干扰素基因刺激因子信号通路，并启动杀死肿瘤细胞的适应性免疫反应。本综述描述了结构，CD47与其配体的功能和相互作用，以及它对吞噬作用和肿瘤细胞命运的调节。它总结了治疗方法，行动机制,靶向CD47的研究进展和挑战。此外,本文概述了靶向CD47的最新治疗方案，如嵌合抗原受体(CAR)T细胞，汽车巨噬细胞和基于纳米技术的输送系统，这对未来靶向CD47的临床研究至关重要。
