The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance.
The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance.
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DOI：
10.3390/vaccines4030022
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发表时间：
2016-06-24
期刊：
影响因子：
7.8
通讯作者：
Palena C
中科院分区：
文献类型：
--
作者：
David JM;Dominguez C;Hamilton DH;Palena C
白细胞介素-8（IL-8，CXCL 8）是由各种细胞类型产生的促炎趋化因子，以将白细胞募集到感染或组织损伤部位。已知IL-8和/或其受体CXCR 1和CXCR 2的获得在肿瘤进展期间是相对常见的。新兴的研究现在表明，肿瘤来源的IL-8的旁分泌信号促进中性粒细胞和骨髓来源的抑制细胞（MDSC）进入肿瘤微环境，这有能力抑制抗肿瘤免疫反应。此外，最近的研究还表明，肿瘤组织产生的IL-8可以诱导肿瘤细胞经历上皮细胞向间充质转化（EMT）的转分化过程，其中肿瘤细胞摆脱上皮细胞特征并获得间充质特征。EMT可增加转移性播散、干性和内在抗性，包括对细胞毒性免疫细胞杀伤的抗性。这篇综述强调了炎症细胞因子IL-8通过增强免疫抑制微环境和激活EMT在促进肿瘤抵抗中发挥的双重潜在作用，然后讨论了靶向IL-8/IL-8受体轴以对抗这些各种抵抗机制的潜力。
Interleukin-8 (IL-8, CXCL8) is a pro-inflammatory chemokine produced by various cell types to recruit leukocytes to sites of infection or tissue injury. Acquisition of IL-8 and/or its receptors CXCR1 and CXCR2 are known to be a relatively common occurrence during tumor progression. Emerging research now indicates that paracrine signaling by tumor-derived IL-8 promotes the trafficking of neutrophils and myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment, which have the ability to dampen anti-tumor immune responses. Furthermore, recent studies have also shown that IL-8 produced by the tumor mass can induce tumor cells to undergo the transdifferentiation process epithelial-to-mesenchymal transition (EMT) in which tumor cells shed their epithelial characteristics and acquire mesenchymal characteristics. EMT can increase metastatic dissemination, stemness, and intrinsic resistance, including to killing by cytotoxic immune cells. This review highlights the dual potential roles that the inflammatory cytokine IL-8 plays in promoting tumor resistance by enhancing the immunosuppressive microenvironment and activating EMT, and then discusses the potential for targeting the IL-8/IL-8 receptor axis to combat these various resistance mechanisms.
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