Thurman Joshua M, Laskowski Jennifer, Nemenoff Raphael A
Division of Nephrology and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Antibodies (Basel). 2020 Nov 5;9(4):61. doi: 10.3390/antib9040061.
Although it was long believed that the complement system helps the body to identify and remove transformed cells, it is now clear that complement activation contributes to carcinogenesis and can also help tumors to escape immune-elimination. Complement is activated by several different mechanisms in various types of cancer, and complement activation fragments have multiple different downstream effects on cancer cells and throughout the tumor microenvironment. Thus, the role of complement activation in tumor biology may vary among different types of cancer and over time within a single tumor. In multiple different pre-clinical models, however, complement activation has been shown to recruit immunosuppressive myeloid cells into the tumor microenvironment. These cells, in turn, suppress anti-tumor T cell immunity, enabling the tumor to grow. Based on extensive pre-clinical work, therapeutic complement inhibitors hold great promise as a new class of immunotherapy. A greater understanding of the role of complement in tumor biology will improve our ability to identify those patients most likely to benefit from this treatment and to rationally combine complement inhibitors with other cancer therapies.
尽管长期以来人们认为补体系统有助于机体识别和清除转化细胞，但现在很清楚，补体激活有助于致癌作用，还能帮助肿瘤逃避免疫清除。在各类癌症中，补体通过几种不同机制被激活，补体激活片段对癌细胞和整个肿瘤微环境具有多种不同的下游效应。因此，补体激活在肿瘤生物学中的作用可能因癌症类型不同以及在单个肿瘤内随时间而有所变化。然而，在多个不同的临床前模型中，补体激活已被证明会将免疫抑制性髓样细胞募集到肿瘤微环境中。这些细胞进而抑制抗肿瘤T细胞免疫，使肿瘤得以生长。基于广泛的临床前研究工作，治疗性补体抑制剂作为一类新型免疫疗法具有很大的前景。对补体在肿瘤生物学中作用的更深入理解将提高我们识别最可能从这种治疗中获益的患者的能力，并使补体抑制剂与其他癌症疗法合理联合使用。
