Department of Laboratory Medicine, Lund University, The Wallenberg Laboratory, Inga Maria Nilssons street 53, 20502 Malmö, Sweden.
Cancer Treat Rev. 2013 Oct;39(6):632-9. doi: 10.1016/j.ctrv.2012.10.008. Epub 2012 Dec 5.
Activation of the complement system by tumor cells was long believed to only benefit the host. Overexpression of complement inhibitors by many tumor cell types and results obtained in several experimental animal models were all in agreement with this hypothesis. However, recent reports imply that the situation is more complex than initially believed and that under certain circumstances tumor cells may use complement to their own advantage, e.g. by recruitment of suppressor T cells or promoting local angiogenesis. Such a dual role of complement may also be apparent when considering the effect of therapeutic monoclonal antibodies (mAb) used to successfully treat B cell malignancies, such as CD20 mAbs. Some argue that besides direct tumor cell killing by mAbs, two main immune effector mechanisms, complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC), may be competing with each other. Experiments aiming at answering the question whether complement is our friend or foe in mAb therapy ended up with seemingly contradictory conclusions. Herein, we revisit the existing knowledge on this pivotal issue based on rituximab and other anti-CD20 mAb as a model of therapeutic agents.
肿瘤细胞激活补体系统长期以来被认为仅有益于宿主。许多肿瘤细胞类型过度表达补体抑制剂的结果和在几种实验动物模型中获得的结果都与这一假说一致。然而，最近的报告表明，情况比最初想象的要复杂，在某些情况下，肿瘤细胞可能会利用补体来获得自身优势，例如通过招募抑制性 T 细胞或促进局部血管生成。在考虑治疗性单克隆抗体（mAb）用于成功治疗 B 细胞恶性肿瘤（如 CD20 mAb）的效果时，这种补体的双重作用也可能显而易见。有人认为，除了 mAb 对肿瘤细胞的直接杀伤作用外，两种主要的免疫效应机制，补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC），可能相互竞争。旨在回答补体在 mAb 治疗中是敌是友的问题的实验最终得出了似乎相互矛盾的结论。在此，我们基于利妥昔单抗和其他抗 CD20 mAb 作为治疗药物的模型，重新审视了这一关键问题的现有知识。
