CXCL9/10/11-CXCR3 轴在肿瘤免疫微环境中的双重作用：机制、治疗意义与临床转化

The signal axis composed of chemokine CXCL9/10/11 and receptor CXCR3 is a key pathway that regulates the migration of immune cells to the tumor microenvironment and affects the anti-tumor immune response. Its functional status is also closely related to the efficacy and drug resistance of immune checkpoint inhibitors (ICIs), but there are many questions about the mechanism and clinical application value of this signal axis.

This signaling axis has a significant bidirectional regulation, and its function is affected by factors such as receptor subtype, expressing cell type, ligand source and tumor progression stage, showing unique spatial and biological specificity: On the one hand, it can recruit effector immune cells such as cytotoxic T cells and natural killer cells, promote the activation of dendritic cells and the formation of tertiary lymphoid structures, and enhance anti-tumor immunity.

On the other hand, it can recruit regulatory T cells, myeloid-derived suppressor cells and other immunosuppressive cells to induce T cell exhaustion and promote tumor immune escape and progression.

In addition, this signaling axis can be used as a predictive biomarker related to tumor immunity. Single-agent or combination therapy targeting this pathway has also shown the potential to overcome immunotherapy resistance, but its clinical translation still faces many obstacles. This review explores the molecular basis of the CXCR3 axis's dual functions, evaluates its potential as a therapeutic target and biomarker in translational medicine, and discusses current obstacles and future directions.