白细胞介素-8与肿瘤免疫逃逸

Interleukin-8 and tumor immune escape

IL-8是趋化因子CXC家族的一员,是一种多细胞来源的细胞因子,在细胞的多种炎症反应中起调节作用,并且在自身免疫性疾病中也发挥重要作用。IL-8通过与细胞膜上的CXC趋化因子受体CXCR1和CXCR2相互作用,激活偶联的G蛋白,由G蛋白进一步激活PLC、AC、PLD、PI3K、JAK2及Ras等信号分子,从而调控基因表达、细胞增殖和分化、细胞代谢、细胞运动及血管生成等多种细胞生命过程。IL-8在多种恶性肿瘤细胞中表达量升高,其高表达与肿瘤细胞增殖、迁移、侵袭、血管生成及上皮间充质转化有密切联系。肿瘤免疫逃逸是肿瘤细胞产生和转移过程中的主要特征之一,肿瘤细胞可以通过多种机制使得人体免疫系统无法对其进行正常的识别和攻击,从而导致肿瘤细胞在体内存活,并且不断增殖和转移,而肿瘤细胞、免疫细胞以及肿瘤微环境中其他相关组分均可以促进肿瘤免疫逃逸。IL-8作为一种炎性趋化因子,已被证明在肿瘤免疫逃逸中具有重要作用,其可通过诱导肿瘤细胞PD-L1表达、抑制肿瘤细胞凋亡、促进肿瘤细胞EMT进程、促进肿瘤微环境血管生成、招募免疫抑制性细胞等五个方面介导肿瘤免疫逃逸。IL-8中和抗体和CXCR1/2拮抗剂在抗肿瘤治疗方面已经显示出较好的治疗效果。

IL-8 is a multicellular cytokine which belongs to the CXC family of chemokines and plays regulatory roles in various inflammatory responses and autoimmune diseases.After binding to CXCR1 and CXCR2,which are members of the transmembrane G-protein coupled receptor family,IL-8 activates the G protein and downstream molecules,such as PLC,AC,PLD,PI3 K,JAK2 and RAS,to regulate gene expression,cell proliferation and differentiation,cell metabolism,cell movement and angiogenesis.IL-8 is over-expressed in various tumors,which is closely related to proliferation,migration,invasion,angiogenesis and EMT of tumors.Tumor immune escape is one critical step in malignant progression of tumors.Tumors develop numerous strategies to escape immune surveillance to proliferate and metastasize.All of the tumor cells,immunosuppressive cells and inflammatory factors within tumor microenvironment facilitate tumor immune escape.As an inflammatory chemokine,IL-8 has been proved to play an important role in tumor immune escape by inducing the expression of PD-L1 in tumor cells,promoting the EMT and angiogenesis,inhibiting the apoptosis of tumor cells and recruiting immunosuppressive cells.IL-8 neutralizing antibodies and CXCR1/2 antagonists have shown certain anti-tumor effects.