Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania 19104, Philadelphia, Pennsylvania, USA.
National Center for Scientific Research 'Demokritos', Athens 15310, Greece.
Nat Rev Immunol. 2018 Jan;18(1):5-18. doi: 10.1038/nri.2017.97. Epub 2017 Sep 18.
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis. It also offers insight into clinical aspects, including the feasibility of using complement biomarkers for cancer diagnosis and the use of complement inhibitors during cancer treatment.
在肿瘤免疫学中,补体传统上被认为是一种辅助成分,可增强基于抗体的免疫疗法(如利妥昔单抗)的细胞溶解作用。值得注意的是,在过去十年的研究中,人们发现了新的分子机制,将肿瘤微环境中失衡的补体激活与炎症和抑制抗肿瘤免疫反应联系起来。这些发现促使人们重新关注通过操纵补体系统进行癌症治疗。本综述总结了我们目前对肿瘤微环境中补体介导的效应功能的理解,重点介绍了补体激活如何作为肿瘤发生的负调节剂或正调节剂发挥作用。它还深入探讨了临床方面的问题,包括使用补体生物标志物进行癌症诊断的可行性,以及在癌症治疗期间使用补体抑制剂的问题。