Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200092, China.
Department of Nephrology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, China.
J Adv Res. 2024 Sep;63:129-158. doi: 10.1016/j.jare.2023.10.009. Epub 2023 Oct 28.
Immunotherapy has emerged as a novel strategy for cancer treatment following surgery, radiotherapy, and chemotherapy. Immune checkpoint blockade and Chimeric antigen receptor (CAR)-T cell therapies have been successful in clinical trials. Cancer cells evade immune surveillance by hijacking inhibitory pathways via overexpression of checkpoint genes. The Cluster of Differentiation 47 (CD47) has emerged as a crucial checkpoint for cancer immunotherapy by working as a "don't eat me" signal and suppressing innate immune signaling. Furthermore, CD47 is highly expressed in many cancer types to protect cancer cells from phagocytosis via binding to SIRPα on phagocytes. Targeting CD47 by either interrupting the CD47-SIRPα axis or combing with other therapies has been demonstrated as an encouraging therapeutic strategy in cancer immunotherapy. Antibodies and small molecules that target CD47 have been explored in pre- and clinical trials. However, formidable challenges such as the anemia and palate aggregation cannot be avoided because of the wide presentation of CD47 on erythrocytes.
This review summarizes the current knowledge on the regulation and function of CD47, and provides a new perspective for immunotherapy targeting CD47. It also highlights the clinical progress of targeting CD47 and discusses challenges and potential strategies.
This review provides a comprehensive understanding of targeting CD47 in cancer immunotherapy, it also augments the concept of combination immunotherapy strategies by employing both innate and adaptive immune responses.
免疫疗法在手术、放疗和化疗之后已成为癌症治疗的新策略。免疫检查点阻断和嵌合抗原受体 (CAR)-T 细胞疗法在临床试验中取得了成功。癌细胞通过过度表达检查点基因来劫持抑制途径，从而逃避免疫监视。分化簇 47 (CD47) 通过作为“不要吃我”信号并抑制先天免疫信号转导，成为癌症免疫治疗的一个重要检查点。此外，CD47 在许多癌症类型中高度表达，通过与吞噬细胞上的 SIRPα 结合，保护癌细胞免受吞噬作用。通过中断 CD47-SIRPα 轴或与其他疗法联合靶向 CD47 已被证明是癌症免疫治疗中的一种有希望的治疗策略。靶向 CD47 的抗体和小分子已在临床前和临床试验中进行了探索。然而，由于 CD47 在红细胞上广泛表达，因此不可避免地会出现贫血和血小板聚集等严重挑战。
本综述总结了 CD47 的调节和功能的现有知识，并为靶向 CD47 的免疫治疗提供了新的视角。它还强调了靶向 CD47 的临床进展，并讨论了挑战和潜在策略。
本综述提供了对癌症免疫治疗中靶向 CD47 的全面理解，它还通过利用先天和适应性免疫反应增强了联合免疫治疗策略的概念。
