| 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
OpenCaryn 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 pageAbstractThe 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.
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发表于 2017-11-24 20:01