Aalinkeel Ravikumar, Quigg Richard J, Alexander Jessy
J Clin Invest. 2025 May 1;135(9). doi: 10.1172/JCI188351.
Kidney cancer poses unique clinical challenges because of its resistance to conventional treatments and its tendency to metastasize. The kidney is particularly susceptible to dysfunction of the complement system, an immune network that tumors often exploit. Recent discoveries have highlighted that the complement system not only plays a crucial role in immune surveillance and defense in the circulatory system, but also functions intracellularly and autonomously. This concept has shifted the focus of investigation toward understanding how complement proteins influence cancer progression by regulating the tumor microenvironment (TME), cell signaling, proliferation, metabolism, and the immune response. With the complement system and its inhibitors emerging as a promising new class of immunotherapeutics and potential complement-targeted treatments advancing through development pipelines and clinical trials, this Review provides a timely examination of how harnessing the complement system could lead to effective tumor treatments and how to strategically combine complement inhibitors with other cancer treatments, offering renewed hope in the fight against kidney cancer.
肾癌因其对传统治疗的抗性以及转移倾向而带来独特的临床挑战。肾脏对补体系统功能障碍尤为敏感，肿瘤常常利用这一免疫网络。最近的发现突出表明，补体系统不仅在循环系统的免疫监视和防御中发挥关键作用，还在细胞内自主发挥功能。这一概念已将研究重点转向了解补体蛋白如何通过调节肿瘤微环境（TME）、细胞信号传导、增殖、代谢和免疫反应来影响癌症进展。随着补体系统及其抑制剂作为一类有前景的新型免疫疗法出现，以及潜在的补体靶向治疗进入研发管道和临床试验，本综述及时审视了利用补体系统如何能带来有效的肿瘤治疗，以及如何将补体抑制剂与其他癌症治疗策略性地联合使用，为抗击肾癌带来新的希望。
