Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
J Hematol Oncol. 2022 Aug 17;15(1):110. doi: 10.1186/s13045-022-01328-x.
Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated immune escape. The most well-described innate immune checkpoints are the "don't eat me" signals, including the CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 axis, and MHC-I/LILRB1 axis. Molecules have been developed to block these pathways and enhance the phagocytic activity against tumors. Several clinical studies have investigated the safety and efficacy of CD47 blockades, either alone or in combination with existing therapy in hematological malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and lymphoma. However, only a minority of patients have significant responses to these treatments alone. Combining CD47 blockades with other treatment modalities are in clinical studies, with early results suggesting a synergistic therapeutic effect. Targeting macrophages with bispecific antibodies are being explored in blood cancer therapy. Furthermore, reprogramming of pro-tumor macrophages to anti-tumor macrophages, and CAR macrophages (CAR-M) demonstrate anti-tumor activities. In this review, we elucidated distinct types of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed.
越来越多的证据表明，先天免疫检查点诱导的吞噬作用检测和清除癌细胞在肿瘤介导的免疫逃逸中起着重要作用。最著名的先天免疫检查点是“别吃我”信号，包括 CD47/signal regulatory protein α 轴（SIRPα）、PD-1/PD-L1 轴、CD24/SIGLEC-10 轴和 MHC-I/LILRB1 轴。已经开发出一些分子来阻断这些途径并增强对肿瘤的吞噬活性。一些临床研究已经调查了 CD47 阻断剂的安全性和疗效，无论是单独使用还是与血液恶性肿瘤（包括骨髓增生异常综合征（MDS）、急性髓系白血病（AML）和淋巴瘤）中的现有疗法联合使用。然而，只有少数患者对这些治疗有明显的反应。CD47 阻断剂与其他治疗方式的联合治疗正在进行临床研究，早期结果表明具有协同治疗效果。双特异性抗体靶向巨噬细胞正在血液癌治疗中进行探索。此外，将促肿瘤巨噬细胞重编程为抗肿瘤巨噬细胞和 CAR 巨噬细胞（CAR-M）显示出抗肿瘤活性。在这篇综述中，我们从临床前实验到临床试验阐述了血液恶性肿瘤中不同类型的巨噬细胞靶向策略，并概述了正在开发的潜在治疗方法。
