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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Mar 31, 2019; 7(3): 80-95
Published online Mar 31, 2019. doi: 10.13105/wjma.v7.i3.80
Prospects for immunotherapy as a novel therapeutic strategy against hepatocellular carcinoma
Yu Akazawa, Toshihiro Suzuki, Toshiaki Yoshikawa, Shoichi Mizuno, Yasunari Nakamoto, Tetsuya Nakatsura
Yu Akazawa, Toshihiro Suzuki, Toshiaki Yoshioka, Shoichi Mizuno, Tetsuya Nakatsura, Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan
Yu Akazawa, Yasunari Nakamoto, Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan
Author contributions: Akazawa Y and Nakatsura T drafted the manuscript; all authors reviewed the manuscript.
Conflict-of-interest statement: Nakatsura T and Suzuki T are supported by fundamental research funding from Ono Pharmaceutical Co., Ltd.; Nakatsura T, Suzuki T and Yoshikawa T are supported by fundamental research funding from Takeda Pharmaceutical Co., Ltd., and BrightPath Biotherapeutics Co., Ltd.; Nakatsura T is supported by fundamental research funding from Noile-Immune Biotech Inc. and Sysmex Co., Ltd. The other authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an 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: Tetsuya Nakatsura, MD, PhD, Doctor, Professor, Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan. tnakatsu@east.ncc.go.jp
Telephone: +81-4-71315490 Fax: +81-4-71336606
Received: February 20, 2019
Peer-review started: February 20, 2019
First decision: March 5, 2019
Revised: March 12, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: March 31, 2019
Processing time: 39 Days and 0.6 Hours
Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, with a poor clinical prognosis. Many standard therapies are often considered for HCC treatment today; however, these conventional therapies often fail to achieve sufficiently effective clinical results. Today, HCC therapy is set to undergo a major revolution, owing to rapid developments in cancer immunotherapy, particularly immune checkpoint inhibitor therapy. Cancer immunotherapy is a novel and promising treatment strategy that differs significantly from conventional therapies in its approach to achieve antitumor effects. In fact, many cancer immunotherapies have been tested worldwide and shown to be effective against various types of cancer; HCC is no exception to this trend. For example, we identified a specific cancer antigen called glypican-3 (GPC3) and performed clinical trials of GPC3-targeted peptide vaccine immunotherapy in patients with HCC. Here, we present an overview of the immune mechanisms for development and progression of HCC, our GPC3-based immunotherapy, and immune checkpoint inhibitor therapy against HCC. Finally, we discuss the future prospects of cancer immunotherapy against HCC. We believe that this review and discussion of cancer immunotherapy against HCC could stimulate more interest in this promising strategy for cancer therapy and help in its further development.

Keywords: Hepatocellular carcinoma; Cancer immunotherapy; Immune checkpoint inhibitor; Glypican-3; Cancer vaccine; Clinical trials; Cytotoxic T-lymphocytes

Core tip: Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, with a poor prognosis. Recent developments and advances in cancer immunotherapy, particularly immune checkpoint inhibitor therapy, could lead to a major paradigm shift in standard HCC therapy. This review aims to provide an overview of novel immunotherapies, including antigen-based immunotherapies such as glypican-3-targeted immunotherapy, and immune checkpoint inhibitor therapy against HCC. It also discusses the future prospects of cancer immunotherapy against HCC.