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Lee et al. Hepatoma Res 2018;4:51 Hepatoma Research
DOI: 10.20517/2394-5079.2018.78

Review Open Access

Cancer immunotherapy for hepatocellular carcinoma

Joo-Ho Lee , Soo-Yeon Oh , Jin Yong Kim , Naoshi Nishida 3
2
1
2
1 Department of Gastroenterology and Hepatology, CHA Bundang Medical Center, CHA University School of Medicine,
Seongnam 13496, South Korea.
2 Department of Gastroenterology, Chaum Life Center, CHA University School of Medicine, Seoul 06062, South Korea.
3 Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Japan.

Correspondence to: Dr. Naoshi Nishida, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine,
Osaka-Sayama 589-8511, Japan. E-mail: naoshi@med.kindai.ac.jp
How to cite this article: Lee JH, Oh SY, Kim JY, Nishida N. Cancer immunotherapy for hepatocellular carcinoma. Hepatoma Res
2018;4:51. http://dx.doi.org/10.20517/2394-5079.2018.78
Received: 13 Jun 2018 First Decision: 11 Jul 2018 Revised: 31 Jul 2018 Accepted: 1 Aug 2018 Published: 10 Sep 2018

Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
Most hepatocellular carcinomas (HCCs) arise on a background of chronically inflamed liver, and thus are considered
typical immunogenic cancers. Although there have been advances in treatment options for HCC, many patients still
struggle with a limited chance of survival requiring further innovative approach. Especially for the advanced HCC, many
other molecular targeted therapies had been evaluated without success. Based on the immunological mechanisms
thought to be acting during HCC development, the effects of diverse immunomodulatory regimens such as therapeutic
vaccination, immune checkpoint inhibitors, and adoptive cellular immunotherapy have been investigated. Notably,
many strategies have been developed in adoptive cellular immunotherapy, including dendritic cells, cytotoxic T cells,
natural killer cells, cytokine-induced killer (CIK) cells, and genetically engineered T cells. In recent clinical trials, adjuvant
CIK cell immunotherapy increased progression free survival after curative treatment of HCC. Most recently, new
immunomodulatory agents were introduced for oncological treatment, eventually leading to the clinical breakthrough
of checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). To
date, very promising published evidence with checkpoint inhibitors in HCC has been reported in the clinical trials with
anti-CTLA-4 agent tremelimumab and a large phase II trial with anti-PD-1 agent nivolumab. Further investigations of
immuno-oncology potentially popularized the applications of immunotherapy in the various stages of HCCs, and thus
immune-based therapies are the promising innovative approach for patients with HCC. Hopefully, the immuno-oncology
will bring about a paradigm shift of anti-cancer treatment for HCC.

Keywords: Hepatocellular carcinoma, adoptive immunotherapy, cytotoxic T lymphocyte associated antigen-4, programmed
cell death 1 protein

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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