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天然免疫检查点CD47-SIRPα在恶性肿瘤中的研究进展

Research Progress of CD47-SIRPα Signaling Axis as An Innate Immune Checkpoint in Cancer

  • 摘要: 针对CTLA-4/B7和PD-1/PD-L1的免疫检查点抑制剂现已广泛应用于临床,其他检查点抑制剂也正在开发中。CD47是广泛表达于正常细胞表面的蛋白质,在肿瘤细胞中呈过表达状态,其受体为髓系抑制性免疫受体SIRPα。阻断CD47与SIRPα之间的相互作用可增强巨噬细胞和中性粒细胞的吞噬作用进而消灭肿瘤细胞。此外,越来越多的证据表明阻断CD47-SIRPα轴还可以增强抗原呈递细胞的功能,从而刺激T细胞介导的抗癌免疫。随着该领域研究的发展,CD47-SIRPα轴的临床应用将会是未来肿瘤免疫治疗的热点之一。

     

    Abstract: Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and PD-1/PD-L1 inhibitory pathways, are now available for clinical use on cancer patients. Other interesting checkpoint inhibitors are currently under the development. CD47 is a protein broadly expressed on the surface of normal cells and often overexpressed in cancer cells, and its receptor is the myeloid inhibitory immunoreceptor SIRPα. Blocking CD47-SIRPα interactions has been shown to promote the destruction of cancer cells by phagocytes, including macrophages and neutrophils. Furthermore, there is growing evidence that targeting CD47-SIRPα axis may also promote antigen-presenting cell function and thereby stimulate T cell-mediated anti-cancer immunity. In summary, with the clinical studies about CD47-SIRPα checkpoint inhibitors expected within the coming years, this is an exciting and rapidly developing field.

     

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