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CXCLs/CXCR2 轴在癌症和炎症性疾病中的潜在作用和靶向治疗。

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases.

机构信息

Laboratory of Aging Research and Nanotoxicology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Laboratory of Aging Research and Nanotoxicology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):289-312. doi: 10.1016/j.bbcan.2019.01.005. Epub 2019 Jan 29.

Abstract

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.

摘要

趋化因子受体 CXCR2 及其配体与肿瘤的进展和各种炎症性疾病有关。CXCLs/CXCR2 轴的激活激活了多种信号通路,包括 PI3K、p38/ERK 和 JAK 通路,并调节细胞存活和迁移。CXCLs/CXCR2 轴在肿瘤微环境中起着至关重要的作用,并招募中性粒细胞到炎症部位。在慢性炎症期间,中性粒细胞的广泛浸润是各种炎症性疾病的最重要的致病因素之一。慢性炎症被认为与癌症的发生密切相关。此外,髓源抑制细胞(MDSCs)对 T 细胞的免疫抑制作用减弱了 T 细胞的抗肿瘤作用,并促进了肿瘤的侵袭和转移。在过去的几十年中,许多针对 CXCR2 的治疗策略显示出了有前途的结果,并进入了临床试验。在这篇综述中,我们重点介绍了 CXCLs/CXCR2 轴的特征和功能,并强调了其在癌症和炎症性疾病中的作用。我们还讨论了它在靶向治疗中的潜在用途。

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