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补体系统在癌症中的作用及其在卵巢癌中的治疗潜力。

Complement system's role in cancer and its therapeutic potential in ovarian cancer.

机构信息

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.

Faculty of Pharmacy, Girne American University, Kyrenia, North Cyprus, Turkey.

出版信息

Scand J Immunol. 2018 Jul;88(1):e12672. doi: 10.1111/sji.12672. Epub 2018 May 23.

Abstract

Cancer immunotherapy is a strong candidate for the long-awaited new edition to standard cancer therapies. For an effective immunotherapy, it is imperative to delineate the players of antitumour immune response. As an important innate immune system effector mechanism, complement is highly likely to play a substantial role in cancer immunity. Studies suggest that there may be two different "states of complement" that show opposing effects on cancer cells; a complement profile that has antitumour effects with low expression of membrane-bound complement regulator proteins (mCRPs), lytic membrane attack complex (MAC) concentration and moderate C5a concentration, and a complement profile that has protumour effects with high expression of mCRPs, sublytic MAC and high concentrations of C5a. One of the cancers that urgently require innovative therapeutic approaches is ovarian cancer, and complement has a potential to be a good target for this purpose. A combinatorial approach where the complement cascade is fine-tuned by inhibiting some of its activities while promoting the others can prove to be a fruitful approach. Herein, we will briefly discuss the cancer-immune system interaction and then present a discussion of complement system's role in tumour immunity and its therapeutic potential for ovarian cancer immunotherapy.

摘要

癌症免疫疗法是期待已久的癌症标准疗法新手段的有力候选者。为了实现有效的免疫疗法,必须明确抗肿瘤免疫反应的参与者。补体作为一种重要的固有免疫系统效应机制,极有可能在癌症免疫中发挥重要作用。研究表明,补体可能存在两种不同的“状态”,对癌细胞表现出相反的作用;一种是具有抗肿瘤作用的补体谱,其特征是膜结合补体调节蛋白(mCRP)、溶细胞攻击复合物(MAC)浓度和中等浓度 C5a 的低表达,另一种是具有促肿瘤作用的补体谱,其特征是 mCRP、亚溶 MAC 和高浓度 C5a 的高表达。迫切需要创新治疗方法的癌症之一是卵巢癌,而补体有可能成为这一目的的良好靶点。通过抑制补体级联反应的某些活性同时促进其他活性来精细调节补体级联反应的组合方法可能是一种富有成效的方法。在此,我们将简要讨论癌症-免疫系统的相互作用,然后讨论补体系统在肿瘤免疫中的作用及其在卵巢癌免疫治疗中的治疗潜力。

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