Department of Medical Oncology, Hubei Cancer Hospital, the Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Colorectal Cancer Clinical Research Center of HuBei Province, Wuhan, China; Colorectal Cancer Clinical Research Center of Wuhan, Wuhan, China.
Department of Gastrointestinal Oncology Surgery, Hubei Cancer Hospital, the Seventh Clinical School Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Colorectal Cancer Clinical Research Center of HuBei Province, Wuhan, China; Colorectal Cancer Clinical Research Center of Wuhan, Wuhan, China.
Cytokine. 2021 Jul;143:155522. doi: 10.1016/j.cyto.2021.155522. Epub 2021 Apr 10.
Complement is an important branch of innate immunity; however, its biological significance goes far beyond the scope of simple nonspecific defense and involves a variety of physiological functions, including the adaptive immune response. In this review, to unravel the complex relationship between complement and tumors, we reviewed the high diversity of complement components in cancer and the heterogeneity of their production and activation pathways. In the tumor microenvironment, complement plays a dual regulatory role in the occurrence and development of tumors, affecting the outcomes of the immune response. We explored the differential expression levels of various complement components in human cancers via the Oncomine database. The gene expression profiling interactive analysis (GEPIA) tool and Kaplan-Meier plotter (K-M plotter) confirmed the correlation between differentially expressed complement genes and tumor prognosis. The tumor immune estimation resource (TIMER) database was used to statistically analyze the effect of complement on tumor immune infiltration. Finally, with a view to the role of complement in regulating T cell metabolism, complement could be a potential target for immunotherapies. Targeting complement to regulate the antitumor immune response seems to have potential for future treatment strategies. However, there are still many complex problems, such as who will benefit from this therapy and how to select the right therapeutic target and determine the appropriate drug concentration. The solutions to these problems depend on a deeper understanding of complement generation, activation, and regulatory and control mechanisms.
补体是先天免疫的一个重要分支；然而，它的生物学意义远不止于简单的非特异性防御，还涉及多种生理功能，包括适应性免疫反应。在这篇综述中，为了阐明补体与肿瘤之间的复杂关系，我们回顾了癌症中补体成分的高度多样性及其产生和激活途径的异质性。在肿瘤微环境中，补体在肿瘤的发生和发展中发挥着双重调节作用，影响着免疫反应的结果。我们通过 Oncomine 数据库探讨了各种补体成分在人类癌症中的差异表达水平。基因表达谱交互分析（GEPIA）工具和 Kaplan-Meier plotter（K-M plotter）证实了差异表达的补体基因与肿瘤预后之间的相关性。肿瘤免疫估计资源（TIMER）数据库用于统计分析补体对肿瘤免疫浸润的影响。最后，鉴于补体在调节 T 细胞代谢中的作用，补体可能是免疫治疗的一个潜在靶点。靶向补体调节抗肿瘤免疫反应似乎具有未来治疗策略的潜力。然而，仍有许多复杂的问题，如谁将从这种治疗中受益，以及如何选择正确的治疗靶点和确定适当的药物浓度。这些问题的解决方案取决于对补体生成、激活以及调节和控制机制的更深入理解。
