Faculty of Medicine, Technion-Institute of Technology, P.O.B. 9697, Haifa 31096, Israel.
Faculty of Medicine, Technion-Institute of Technology, P.O.B. 9697, Haifa 31096, Israel.
Cytokine. 2018 Sep;109:24-28. doi: 10.1016/j.cyto.2018.02.012. Epub 2018 Feb 12.
Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication.
趋化因子主要因其趋化特性而闻名,而其指导靶细胞(包括 T 细胞)生物学功能的能力则鲜为人知。本综述重点介绍了一种名为 CXCL10 的关键趋化因子,及其在癌症和炎症性自身免疫中指导 CD4+和 CD8+T 细胞迁移特性和生物学功能的作用。CXCR3 是一种趋化因子受体,在 CD4+T 细胞、CD8+T 细胞和 NK 细胞中大量表达。它有三个已知的配体:CXCL9、CXCL10 和 CXCL11。包括我们实验室在内的不同研究表明,除了吸引 CD8+和 CD4+效应 T 细胞到肿瘤部位和炎症部位外,CXCL10 还指导这些细胞的极化并增强其生物学功能。这使得 CXCL10 成为一种“关键驱动趋化因子”,也是治疗炎症性肠病、多发性硬化症、类风湿关节炎等自身免疫性疾病的有效靶点。对于癌症,这促使包括我们小组在内的不同团队开发基于 CXCL10 的癌症疗法,因为它能够增强 T 细胞依赖的抗肿瘤免疫。本综述总结了这些发现及其潜在的转化意义。