CCL2^-CCR2 信号轴在肿瘤进展中的研究进展

Research Progress of CCL2-CCR2 Signaling Axis in Tumor Progression

摘要

CC 趋化因子配体 2（C-C chemokine ligand 2，CCL2）及其受体 CCR2 参与多种癌症的发生及发展，近年来已成为肿瘤免疫治疗的研究热点。在肿瘤微环境中，CCL2-CCR2 轴的激活不仅促进免疫抑制表型巨噬细胞的迁移，还可通过多种机制加剧癌症进展，如增加肿瘤细胞的增殖与侵袭、诱导血管生成和募集免疫抑制细胞以促进肿瘤的发生、发展及免疫逃逸。针对 CCL2-CCR2 信号通路开展的实体瘤和转移性肿瘤临床试验，进一步验证了该信号通路在癌症进展中的关键作用。综述 CCL2-CCR2 轴的结构与功能及其在肿瘤微环境和癌症进展中的作用机制，并结合目前临床前及临床研究结果探讨靶向 CCL2-CCR2 轴的治疗策略，旨在为用于癌症治疗的 CCL2/CCR2 抑制剂开发提供参考。

Abstract

C-C chemokine ligand 2 (CCL2) and its receptor CCR2 are involved in the initiation and progression of various cancers, and have become a research hotspot in tumor immunotherapy. In the tumor microenvironment, activation of the CCL2-CCR2 axis not only promotes the migration of immunosuppressive macrophages but also exacerbates cancer progression through multiple mechanisms such as enhancing tumor cell proliferation and invasion, inducing angiogenesis, and recruiting immunosuppressive cells to promote tumor initiation, development, and immune evasion. Clinical trials targeting the CCL2-CCR2 signaling pathway in solid tumors and metastatic cancers have further validated its critical role in cancer progression. This review summarizes the structure and function of the CCL2-CCR2 axis, its role in the tumor microenvironment and cancer progression, and discusses current preclinical and clinical research on targeted therapies against the CCL2-CCR2 axis, aiming to provide some insights for the development of CCL2/CCR2 inhibitors for cancer treatment.

关键词

趋化因子 / CCL2-CCR2 信号轴 / 肿瘤免疫 / 巨噬细胞

Key words

chemokine / CCL2-CCR2 signaling axis / tumor immunology / macrophage

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