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CXCL9、CXCL10、CXCL11/CXCR3免疫激活轴——新型癌症治疗的靶点

CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy.

作者信息

Tokunaga Ryuma, Zhang Wu, Naseem Madiha, Puccini Alberto, Berger Martin D, Soni Shivani, McSkane Michelle, Baba Hideo, Lenz Heinz-Josef

机构信息

Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, United States.

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 8608556, Japan.

出版信息

Cancer Treat Rev. 2018 Feb;63:40-47. doi: 10.1016/j.ctrv.2017.11.007. Epub 2017 Nov 26.

DOI:10.1016/j.ctrv.2017.11.007
PMID:29207310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5801162/
Abstract

Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in anti-tumor immune response in the cancer environment is of great interest. Although immunotherapy has shown clinical benefit for some cancer patients, other patients do not respond. One of the mechanisms of resistance to checkpoint inhibitors may be chemokine signaling. The CXCL9, -10, -11/CXCR3 axis regulates immune cell migration, differentiation, and activation, leading to tumor suppression (paracrine axis). However, there are some reports that show involvements of this axis in tumor growth and metastasis (autocrine axis). Thus, a better understanding of CXCL9, -10, -11/CXCR3 axis is necessary to develop effective cancer control. In this article, we summarize recent evidence regarding CXCL9, CXCL10, CXCL11/CXCR3 axis in the immune system and discuss their potential role in cancer treatment.

摘要

趋化因子是一类能诱导趋化作用、促进免疫细胞分化并导致组织外渗的蛋白质。鉴于这些特性，它们在癌症环境中的抗肿瘤免疫反应中的作用备受关注。尽管免疫疗法已对一些癌症患者显示出临床益处，但其他患者并无反应。对检查点抑制剂产生抗性的机制之一可能是趋化因子信号传导。CXCL9、-10、-11/CXCR3轴调节免疫细胞的迁移、分化和激活，从而导致肿瘤抑制（旁分泌轴）。然而，有一些报道表明该轴参与肿瘤生长和转移（自分泌轴）。因此，为了开发有效的癌症控制方法，有必要更好地了解CXCL9、-10、-11/CXCR3轴。在本文中，我们总结了关于免疫系统中CXCL9、CXCL10、CXCL11/CXCR3轴的最新证据，并讨论了它们在癌症治疗中的潜在作用。

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本文引用的文献

[1]
Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer.

Oncotarget. 2017-7-18

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Cancer Res. 2017-5-18

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Br J Cancer. 2016-8-23

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Gastroenterology. 2016-11

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J Immunol. 2016-9-1

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Oncol Rep. 2016-9

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Br J Cancer. 2016-7-12

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Oncoimmunology. 2015-10-29

[10]
Inhibition of DPP4 activity in humans establishes its in vivo role in CXCL10 post-translational modification: prospective placebo-controlled clinical studies.

EMBO Mol Med. 2016-6-1

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