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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2019; 25(24): 2977-2989
Published online Jun 28, 2019. doi: 10.3748/wjg.v25.i24.2977
Immunotherapy for hepatocellular carcinoma: Current and future
Michael P Johnston, Salim I Khakoo
Michael P Johnston, Department of Hepatology, Southampton General Hospital, University Hospital Southampton, Southampton SO16 6YD, United Kingdom
Salim I Khakoo, Department of Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, United Kingdom
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected byan in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Salim I Khakoo, FRCP (C), MBBS, MD, Professor, Department of Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Mailpoint 811, Level E South Academic Block, Tremona Road, Southampton SO16 6YD, United Kingdom. s.i.khakoo@soton.ac.uk
Telephone: +44-23-8077-7222
Received: March 30, 2019
Peer-review started: April 1, 2019
First decision: April 16, 2019
Revised: April 24, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: June 28, 2019
Processing time: 90 Days and 23.3 Hours
Abstract

Hepatocellular carcinoma (HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However, there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy, either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.

Keywords: Adoptive cell therapy; Cancer vaccine; Checkpoint inhibitor; Hepatocellular carcinoma; Immunotherapy; Liver cancer; Oncolytic virus

Core tip: A significant proportion of patients with hepatocellular carcinoma (HCC) present with advanced disease, for which there are limited systemic therapeutic options. Complicating this, HCC often develops on a background of cirrhosis, which can preclude the use of certain cytotoxic agents. Immunotherapy has previously not been an available therapeutic option in HCC. However, checkpoint inhibition therapy was recently licensed as a second line option for advanced disease. Multiple other promising agents are in development which boost existing immune response or stimulate a de novo immune response. These agents are discussed herein.