Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain; Cancer Center University of Navarra (CCUN), Pamplona, Spain; University of Navarra, School of Sciences, Department of Biochemistry and Genetics, Pamplona, Spain.
Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain; Cancer Center University of Navarra (CCUN), Pamplona, Spain; University of Navarra, School of Medicine, Department of Pathology, Anatomy and Physiology, Pamplona, Spain.
Cancer Lett. 2022 Nov 28;549:215900. doi: 10.1016/j.canlet.2022.215900. Epub 2022 Sep 8.
Tumor progression relies on the interaction between tumor cells and their surrounding tumor microenvironment (TME), which also influences therapeutic responses. The complement system, an essential part of innate immunity, has been traditionally considered an effector arm against tumors. However, established tumors co-opt complement-mediated immune responses in the TME to support chronic inflammation, activate cancer-related signaling pathways and hamper antitumor immune responses. In this context, myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors with immunosuppressive functions, are recognized as major mediators of tumor-associated complement activities. This review focuses on the impact of complement activation within the TME, with a special emphasis on MDSC functions and the involvement of the C5a/C5aR1 axis. We also discuss the translation of these findings into therapeutic advances based on complement inhibition.
肿瘤的进展依赖于肿瘤细胞与其周围肿瘤微环境（TME）的相互作用，这也影响治疗反应。补体系统是先天免疫的重要组成部分，传统上被认为是对抗肿瘤的效应器臂。然而，已建立的肿瘤会利用 TME 中的补体介导的免疫反应来支持慢性炎症、激活与癌症相关的信号通路并阻碍抗肿瘤免疫反应。在这种情况下，髓系来源的抑制细胞（MDSC），一种具有免疫抑制功能的异质性髓系祖细胞群体，被认为是与肿瘤相关的补体活性的主要介质。本综述重点讨论了 TME 内补体激活的影响，特别强调了 MDSC 的功能以及 C5a/C5aR1 轴的参与。我们还讨论了将这些发现转化为基于补体抑制的治疗进展。
