Complement and Inflammation Research Section, DIR, NHLBI, NIH, Bethesda, MD, 20892, United States.
Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, 79601, United States.
Semin Immunol. 2018 Jun;37:85-97. doi: 10.1016/j.smim.2018.02.003. Epub 2018 Feb 15.
Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response. The discovery of functional intracellular complement and its roles in cellular metabolism opened novel avenues for research and potential therapeutic implications. The recent studies demonstrating immunoregulatory functions of complement in the tumor microenvironment and the premetastatic niche shifted the paradigm on our understanding of functions of the complement system in regulating immunity. Several complement proteins, through their interaction with cells in the tumor microenvironment and in metastasis-targeted organs, contribute to modulating tumor growth, antitumor immunity, angiogenesis, and therefore, the overall progression of malignancy and, perhaps, responsiveness of cancer to different therapies. Here, we focus on recent progress in our understanding of immunostimulatory vs. immunoregulatory functions of complement and potential applications of these findings to the design of novel therapies for cancer patients.
补体最初被发现是作为一组血浆蛋白，“补充”抗体的细胞溶解活性。然而，我们目前的知识将这一由几种血浆蛋白、受体和调节剂组成的复杂系统置于先天免疫的中心，作为初始先天反应和适应性免疫反应之间的桥梁。因此，补体似乎是消除病原体的关键，不仅作为早期反应防御，而且通过指导随后的适应性免疫反应。功能性细胞内补体的发现及其在细胞代谢中的作用为研究和潜在的治疗意义开辟了新途径。最近的研究表明，补体在肿瘤微环境和前转移龛中的免疫调节功能改变了我们对补体系统在调节免疫方面的功能的理解模式。几种补体蛋白通过与肿瘤微环境中的细胞以及转移靶向器官中的细胞相互作用，有助于调节肿瘤生长、抗肿瘤免疫、血管生成，从而整体上调节恶性肿瘤的进展，以及癌症对不同治疗方法的反应性。在这里，我们重点介绍我们对补体的免疫刺激与免疫调节功能的理解的最新进展，以及这些发现对设计癌症患者新型治疗方法的潜在应用。
