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标题: 免疫检查点抑制：预防和治疗肝细胞癌的前景 [打印本页]

作者: StephenW 时间: 2017-11-24 20:01 标题: 免疫检查点抑制：预防和治疗肝细胞癌的前景

Review

Citation: Clinical & Translational Immunology (2017) 6, e161; doi:10.1038/cti.2017.47
Published online 10 November 2017

Immune checkpoint inhibition: prospects for prevention and therapy of hepatocellular carcinoma
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Caryn L Elsegood1, Janina EE Tirnitz-Parker1, John K Olynyk1,2,3 and George CT Yeoh4,5

1School of Biomedical Science, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
2Department of Gastroenterology and Hepatology, Fiona Stanley and Fremantle Hospitals, South Metropolitan Health Service, Murdoch, Western Australia, Australia
3School of Health and Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
4School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia
5Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia

Correspondence: Dr CL Elsegood, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia. E-mail: [email protected]

Received 3 October 2016; Revised 10 August 2017; Accepted 10 September 2017

Top of pageAbstract

The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present. However, the tolerogenic nature of the liver means that the immune response to infection, chronic inflammation and tumour cells within the hepatic environment is usually ineffective. Here we review the roles that immune cells and cytokines have in the development of the most common primary liver cancer, hepatocellular carcinoma (HCC). We then examine how the immune system may be subverted throughout the stages of HCC development, particularly with respect to immune inhibitory molecules, also known as immune checkpoints, such as programmed cell death protein-1, programmed cell death 1 ligand 1 and cytotoxic T lymphocyte antigen 4, which have become therapeutic targets. Finally, we assess preclinical and clinical studies where immune checkpoint inhibitors have been used to modify disease during the carcinogenic process. In conclusion, inhibitory molecule-based immunotherapy for HCC is in its infancy and further detailed research in relevant in vivo models is required before its full potential can be realised.

作者: StephenW 时间: 2017-11-24 20:04

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引用：Clinical＆Translational Immunology（2017）6，e161; DOI：10.1038 / cti.2017.47
2017年11月10日在线发布
免疫检查点抑制：预防和治疗肝细胞癌的前景
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Caryn L Elsegood1，Janina EE Tirnitz-Parker1，John K Olynyk1,2,3和George Yeoh4,5

1澳大利亚西澳大利亚州科廷科廷科廷科廷健康创新研究院生物医学院
2澳大利亚西澳大利亚Murdoch南部大都会卫生服务部Fiona Stanley和Fremantle医院消化内科和肝病科
3伊迪斯科文大学健康和医学科学学院，澳大利亚西澳大利亚州Joondalup
4西澳大学化学与生物化学学院，澳大利亚西澳大利亚克劳利
哈里珀金斯医学研究所，QEII医学中心，Nedlands和西澳大学医学研究中心，西澳大利亚克劳利

通讯地址：澳大利亚西澳大利亚州珀斯GPO Box U1987，科廷大学科廷医学创新研究所生物医学科学学院CL Elsegood博士。电子邮件：[email protected]

2016年10月3日获得2017年8月10日修订;接受2017年9月10日
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全球肝癌患病率迅速上升，这主要是由于近几十年来病毒性肝炎，酗酒和肥胖的发病率增加所致。索拉非尼作为晚期不可切除的肝细胞癌的金标准，但对生存时间的改善极其有限，所以对于肝癌的治疗选择受到显着限制。免疫系统现在被认为是癌症发展的关键调节者，其通过其防止感染和慢性炎症（其促进癌症发展）并消除存在时的肿瘤细胞的能力。然而，肝脏的致耐受性意味着对肝脏环境中的感染，慢性炎症和肿瘤细胞的免疫应答通常是无效的。在这里，我们回顾了免疫细胞和细胞因子在最常见的原发性肝癌，肝细胞癌（HCC）发展中的作用。然后，我们研究在整个HCC发展阶段免疫系统如何被破坏，特别是免疫抑制分子，也称为免疫检查点，如程序性细胞死亡蛋白-1，程序性细胞死亡1配体1和细胞毒性T淋巴细胞抗原4，已成为治疗的目标。最后，我们评估在致癌过程中免疫检查点抑制剂已被用于修饰疾病的临床前和临床研究。总之，HCC的抑制性分子免疫治疗尚处于起步阶段，在其相关的体内模型的研究中还需要进一步的研究，才能发挥其潜力。

作者: StephenW 时间: 2017-11-24 20:05

http://www.nature.com/cti/journal/v6/n11/full/cti201747a.html

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