趋化因子是一种可以由肿瘤细胞和基质细胞产生的小分子分泌蛋白，趋化因子受体在肿瘤细胞和基质细胞表面也均有表达，趋化因子和其相配对的同源受体结合通过直接和间接方式调控肿瘤生长，包括激活信号通路直接调控肿瘤细胞的增殖与转移、作用于血管内皮细胞间接调控肿瘤及协调免疫细胞在组织内的迁移和定位后影响免疫反应调控肿瘤。趋化因子分为CXC、CC、CX3C及C四大类，研究较多的亚型为CXC和CC。鉴于CXC趋化因子及其受体在恶性肿瘤中作用广泛，且与免疫系统关系密切，有望成为一个有潜力的治疗靶标，其与免疫检查点抑制剂联合作用于肿瘤微环境（tumor microenvironment，TME），改善肿瘤免疫反应。本文对CXC亚型的趋化因子/趋化因子受体轴研究进展进行综述，包括促肿瘤轴CXCR2/CXCLs、CXCR4/CXCL12 和抑肿瘤轴CXCR3/CXCL9~11 的基本生物学特性、对肿瘤的直接作用、对TME的间接作用、靶向治疗以及这3 个轴所包含的受体及配体的预测预后意义。

Chemokines are small secreted proteins produced by cancer and stromal cells. Chemokine receptors are also expressed on the surface of tumor cells and stromal cells. Chemokines bind to their homologous receptors to regulate tumor growth directly and indirectly, including direct regulation of tumor proliferation and metastasis by activating signal pathway, indirect regulation of tumor through acting on vascular endothelial cells and regulating immune response by coordinating the migration and localization of immune cells in tissues. Chemokines can be divided into four categories: CXC, CC, CX3C and C, among which CXC and CC are the most studied subtypes. In view of the fact that CXC chemokines and their receptors play a wide range of roles in malignant tumors and are closely related to the immune system, they are expected to become potential therapeutic targets, to improve tumor immune response by combining with immune checkpoint inhibitors to act in tumor microenvironment (TME). This paper reviews the research progress on chemokine/chemokine receptor axis of CXC subtypes, including the basic biological characteristics of tumor-promoting axis CXCR2/CXCLs, CXCR4/CXCL12 and tumor-suppressing axis CXCR3/CXCL9-11, their direct effect on tumor, indirect effect on TME, targeted therapy and prognostic significance of the receptors and ligands contained in these three axes.

山西省自然科学基金资助项目（No.201901D111421)