Department of Medicine, ICCE Institute, Department of Pathology and Immunology, Siteman Cancer Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Department of Immunology, Department of Breast Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Nat Rev Immunol. 2019 Jun;19(6):369-382. doi: 10.1038/s41577-019-0127-6.
Macrophages are critical mediators of tissue homeostasis, with tumours distorting this proclivity to stimulate proliferation, angiogenesis and metastasis. This had led to an interest in targeting macrophages in cancer, and preclinical studies have demonstrated efficacy across therapeutic modalities and tumour types. Much of the observed efficacy can be traced to the suppressive capacity of macrophages, driven by microenvironmental cues such as hypoxia and fibrosis. As a result, tumour macrophages display an ability to suppress T cell recruitment and function as well as to regulate other aspects of tumour immunity. With the increasing impact of cancer immunotherapy, macrophage targeting is now being evaluated in this context. Here, we discuss the results of clinical trials and the future of combinatorial immunotherapy.
巨噬细胞是组织动态平衡的关键介质,肿瘤会扭曲这种促进增殖、血管生成和转移的倾向。这导致人们对癌症中靶向巨噬细胞产生了兴趣,临床前研究已经证明了多种治疗方式和肿瘤类型的疗效。观察到的大部分疗效可以追溯到巨噬细胞的抑制能力,这是由缺氧和纤维化等微环境线索驱动的。因此,肿瘤巨噬细胞表现出抑制 T 细胞募集和功能的能力,并调节肿瘤免疫的其他方面。随着癌症免疫疗法的影响不断增加,现在正在这方面评估巨噬细胞靶向治疗。在这里,我们讨论临床试验的结果和组合免疫疗法的未来。