Zhou Xuefei, Liu Xiangrui, Huang Leaf
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
Adv Funct Mater. 2021 Jan 27;31(5). doi: 10.1002/adfm.202006220. Epub 2020 Nov 10.
Macrophages are one of the most abundant non-malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor-specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti-phagocytic molecules, such as CD47. In addition, macrophages also rapidly recognize and engulf apoptotic cells (efferocytosis) in the tumor microenvironment, which inhibits inflammatory responses and facilitates immune escape of tumor cells. Thus, intervention of macrophage phagocytosis by blocking anti-phagocytic signals on live tumor cells or inhibiting tumor efferocytosis presents a promising strategy for the development of cancer immunotherapies. Here, the regulation of macrophage-mediated tumor cell phagocytosis is first summarized, followed by an overview of strategies targeting macrophage phagocytosis for the development of antitumor therapies. Given the potential off-target effects associated with the administration of traditional therapeutics (for example, monoclonal antibodies, small molecule inhibitors), we highlight the opportunity for nanomedicine in macrophage phagocytosis intervention.
巨噬细胞是肿瘤微环境中最丰富的非恶性细胞之一，在介导肿瘤免疫中发挥关键作用。作为重要的固有免疫细胞，巨噬细胞具有吞噬肿瘤细胞并呈递肿瘤特异性抗原以诱导适应性抗肿瘤免疫的潜力，这使得针对巨噬细胞吞噬作用进行癌症免疫治疗越来越受到关注。然而，活肿瘤细胞已通过广泛表达抗吞噬分子（如CD47）来逃避巨噬细胞的吞噬。此外，巨噬细胞还能迅速识别并吞噬肿瘤微环境中的凋亡细胞（胞葬作用），这会抑制炎症反应并促进肿瘤细胞的免疫逃逸。因此，通过阻断活肿瘤细胞上的抗吞噬信号或抑制肿瘤胞葬作用来干预巨噬细胞吞噬作用，是开发癌症免疫疗法的一种有前景的策略。在此，首先总结巨噬细胞介导的肿瘤细胞吞噬作用的调控，接着概述针对巨噬细胞吞噬作用开发抗肿瘤疗法的策略。鉴于传统疗法（如单克隆抗体、小分子抑制剂）给药可能存在的脱靶效应，我们强调了纳米医学在巨噬细胞吞噬作用干预方面的机遇。
