Division of Molecular Oncology and Immunology, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Medical Oncology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Immunity. 2020 May 19;52(5):742-752. doi: 10.1016/j.immuni.2020.04.011.
The cytotoxic activity of myeloid cells is regulated by a balance of signals that are transmitted through inhibitory and activating receptors. The Cluster of Differentiation 47 (CD47) protein, expressed on both healthy and cancer cells, plays a pivotal role in this balance by delivering a "don't eat me signal" upon binding to the Signal-regulatory protein alpha (SIRPα) receptor on myeloid cells. Here, we review the current understanding of the role of the CD47-SIRPα axis in physiological tissue homeostasis and as a promising therapeutic target in, among others, oncology, fibrotic diseases, atherosclerosis, and stem cell therapies. We discuss gaps in understanding and highlight where additional insight will be beneficial to allow optimal exploitation of this myeloid cell checkpoint as a target in human disease.
髓系细胞的细胞毒性活性受通过抑制性和激活性受体传递的信号的平衡调节。分化簇 47（CD47）蛋白在健康细胞和癌细胞上均表达，通过与髓系细胞上的信号调节蛋白 alpha（SIRPα）受体结合传递“不要吃我信号”，在这种平衡中发挥关键作用。在这里，我们回顾了 CD47-SIRPα 轴在生理组织稳态中的作用及其作为一种有前途的治疗靶点的作用，特别是在肿瘤学、纤维化疾病、动脉粥样硬化和干细胞治疗中。我们讨论了理解上的差距，并强调了需要额外的见解将如何有益于将这种髓系细胞检查点作为人类疾病的靶点进行最佳利用。
