CD47分子与抗肿瘤免疫

The Role of CD47 in Anti-tumor Immune Response

肿瘤进展与人免疫系统间的联系已经被广泛研究,有许多免疫分子已被证实参与其中。CD47(整合素相关蛋白)为一种免疫球蛋白超家族成员,在人免疫系统中发挥着重要功能。研究表明CD47在肿瘤细胞表面也有高表达,其高表达与肿瘤的生长、转移及复发等密切相关。肿瘤细胞表面的CD47与巨噬细胞表面的SIRPα相互作用,并发出"别吃我"的免疫抑制性信号,从而保护肿瘤细胞免受巨噬细胞吞噬。因此,开发以CD47为靶点的拮抗剂可阻断此抑制性信号,从而增强巨噬细胞的吞噬效应,以达到增强抗肿瘤免疫反应的目的。最新研究证实,CD47拮抗剂在T细胞介导的抗肿瘤免疫反应中也发挥了重要作用。本文将对CD47分子的结构功能、在抗肿瘤免疫反应中的作用及以其为靶点的拮抗剂研究进展进行综述,以期为进一步的药物开发及临床研究等提供参考。

The relationship between immune system and tumor progression has been widely investigated.Various molecules have been verified to participate in the process. CD47,a universally expressed member of the immunoglobulin superfamily,plays an important role in human immune system. Many studies revealed that CD47 was also highly expressed on the surface of cancer cells including acute myeloid leukemia（ AML）,non-Hodgkin lymphoma（ NHL）,bladder cancer and breast cancer. The overexpression of CD47 was found to be associated with tumor growth, migration and recurrence.Recently,CD47 blockade has been as another immune checkpoint therapy for cancer. CD47-mediated interaction with SIRPα initiates a distinct immune inhibitory ＂Don＇t eat me＂signal transduction cascade resulting in inhibition of phagocytosis. Recent studies showed that antibodies or other fusion proteins targeting CD47 have great potential to enhance the anti-tumor immune responses,which may exert its activity by blocking the inhibitory ＂Don ＇t eat me ＂signal and activating the phagocytosis potency of macrophages. More recently,researchers showed that CD47 antagonists could drive T cell-mediated elimination of immunogenic tumors. In conclusion,CD47-targeting agents have the potential to enhance anti-tumor immune responses by simultaneously activating macrophages and CD8＋T cells. In thisreview,we summarized the structure and function of CD47 and its role in anti-tumor immune response.Moreover,we discussed the antagonists targeting CD47 to provide a new strategy for future drug development and clinical study. As a promising anti-tumor therapeutic target,more attentions should be paid to CD47,especially for its application in the treatment of cancers.