Sim Tao Ming, Chng Wee Joo, Liu Haiyan, de Mel Sanjay
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore.
Discov Oncol. 2025 Aug 25;16(1):1616. doi: 10.1007/s12672-025-03312-6.
Immune evasion is a hallmark of cancer and there is mounting evidence that the tumor microenvironment (TME) plays a role in the pathogenesis of haematologic malignancies as well as treatment resistance. Macrophages play a central role in anti-tumor immunity, and dysregulation of macrophage mediated phagocytosis has recently emerged as a key player in blood cancers. The integrin associated protein CD47 is expressed in a variety of cancers and interacts with its ligand, signal regulatory protein α (SIRPα) expressed on macrophages, resulting in down regulation of macrophage-mediated phagocytosis. CD47 is highly expressed in various cancers including multiple myeloma (MM). It is therefore postulated that blockade of the CD47-SIRPα immune checkpoint has the potential to 're-awaken' macrophage mediated phagocytosis of MM plasma cells. In this review, we provide our perspective on the key pre-clinical data supporting the CD47-SIRPα axis as a therapeutic target in MM. We subsequently discuss the ongoing clinical trials which may provide the basis for future clinical translation of these agents. We also highlight key gaps in our knowledge of macrophage biology in MM which need to be addressed by future research. Finally, we present potential future directions for translational research and personalized application of macrophage-based immunotherapy in MM.
免疫逃逸是癌症的一个标志，越来越多的证据表明肿瘤微环境（TME）在血液系统恶性肿瘤的发病机制以及治疗耐药性中发挥作用。巨噬细胞在抗肿瘤免疫中起核心作用，巨噬细胞介导的吞噬作用失调最近已成为血液癌症的关键因素。整合素相关蛋白CD47在多种癌症中表达，并与其在巨噬细胞上表达的配体信号调节蛋白α（SIRPα）相互作用，导致巨噬细胞介导的吞噬作用下调。CD47在包括多发性骨髓瘤（MM）在内的各种癌症中高度表达。因此，推测阻断CD47-SIRPα免疫检查点有可能 “重新唤醒” 巨噬细胞介导的MM浆细胞吞噬作用。在这篇综述中，我们阐述了支持将CD47-SIRPα轴作为MM治疗靶点的关键临床前数据的观点。随后，我们讨论了正在进行的临床试验，这些试验可能为这些药物未来的临床转化提供依据。我们还强调了在MM巨噬细胞生物学知识方面的关键空白，这需要未来的研究加以解决。最后，我们提出了MM中基于巨噬细胞的免疫疗法转化研究和个性化应用的潜在未来方向。
