Research progress of drugs for cancer immunotherapy based on CCL2/CCR2 signaling axis
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摘要:
趋化因子配体2（C-C motif chemokine ligand 2，CCL2）及其受体CCR2与肿瘤的发生、发展密切相关。CCL2/CCR2信号轴通过多种机制促进肿瘤进展，一方面CCL2与肿瘤细胞表面的CCR2结合促进肿瘤的生长/存活和转移；更为重要的是CCL2可以招募多种免疫抑制细胞在肿瘤微环境中聚集，抑制免疫细胞的功能和活性，促进肿瘤进展。本文综述了CCL2/CCR2信号轴以及其在肿瘤及肿瘤微环境中的作用，并重点介绍了靶向CCL2/CCR2信号轴药物的临床研究进展，以期深入并全面了解CCL2/CCR2信号轴在肿瘤进展中的作用机制，开发更有效的肿瘤免疫治疗药物。
Abstract:C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 are closely related to tumorigenesis and tumor progression. The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms: CCL2 binds to CCR2 on the surface of tumor cells, and thus promotes tumor growth/survival and metastasis; more importantly, CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment, and inhibits the function and activity of immune cells, promoting tumor progression. The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment, with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis, in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.
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Keywords:
- CCL2 /
- CCR2 /
- cancer immunotherapy /
- tumor microenvironment /
- immunosuppressive cells
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Figure 1. CCL2/CCR2 signaling axis in tumor progression. Once CCL2 binds to CCR2 receptor on the surface of tumor cells, a series of downstream transduction pathways are activated, such as JAK/STAT, PI3K/AKT，MAPK and Hedgehog，promoting the growth, proliferation, survival, migration/invasion, angiogenesis of tumor cells
CCL2: C-C motif chemokine ligand 2; CCR2: C-C motif chemokine receptor 2; JAK: Janus kinase; STAT3/5: Signal transducer and activator of transcription 3/5; Smo: Smoothened; Gli-1: Gli family zinc finger 1; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B(PKB); mTORC1: Mechanistic target of rapamycin complex 1; PARP: poly ADP-ribose polymerase; RAS/RAF: Rat sarcoma/Rapidly accelerated fibrosarcoma; MEK1/2: Mitogen-activated extracellular signal-regulated kinase1/2; ERK1/2: Extracellular signal-regulated kinase1/2
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Figure 2. Role of the CCL2/CCR2 signaling axis in the tumor microenvironment
NK cell: Natural killer cell; T cell: T-lymphocyte; DC cell: Dendritic cell; MDSC: Myeloid-derived suppressor cell; Treg: Regulatory T cells; TAM: Tumor-associated macrophages; TAN: Tumor-associated neutrophil; CAF: Cancer-associated fibroblasts; ECs: Endothelial cells; Th2: Helper T lymphocyte 2
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