IL-8与肿瘤免疫的研究进展

Progress in understanding of relationship between IL-8 and tumor immunity

IL-8是最早被发现的趋化性细胞因子,在结肠癌、乳腺癌、黑色素瘤、卵巢癌等多种实体瘤中表达上调。IL-8-CXCR1/2信号通路可通过激活JAK/STAT、PI3K/Akt等多种信号通路,促进免疫抑制性细胞向肿瘤微环境的浸润、血管生成、上皮-间充质转化、干性表型的获得等过程,进一步促进肿瘤的生长、侵袭、转移及耐药性。目前认为IL-8是调节肿瘤微环境的关键因子。越来越多的研究关注IL-8-CXCR1/2信号通路相关的抗肿瘤治疗。本文就IL-8-CXCR1/2信号通路在肿瘤发生、发展、转移及免疫抑制的作用及靶向IL-8-CXCR1/2信号通路的研究进展作一综述。

Interleukin(IL)-8 is the first discovered chemotactic cytokine,and its expression is upregulated in a variety of solid tumors such as colorectal cancer,breast cancer,melanoma,and ovarian cancer.Recent studies have shown that the IL-8-CXCR1/2 axis can promote the infiltration of immunosuppressive cells,such as myeloid-derived suppressor cells,into the tumor microenvironment,angiogenesis,epithelialmesenchymal transition,and the acquisition of stem-like phenotypes by activating JAK/STAT,PI3K/Akt,and other signaling pathways.These signaling pathways can further promote tumor growth,invasion,metastasis,and drug resistance.Recently,IL-8 is considered to be a key factor in the regulation of the tumor microenvironment.More and more preclinical data suggest that blockade of the IL-8-CXCR1/2 axis can enhance the tumor killing function of T cells and NK cells.The combining of inhibition of the IL-8-CXCR1/2 axis with immune checkpoint inhibitors may be a promising treatment strategy for tumor.Here,we review the role of the IL-8-CXCR1/2 signaling pathway in tumor occurrence,development,metastasis,and immunosuppression,and the research and clinical trials of drugs targeting the IL-8-CXCR1/2 signaling pathway.