Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2021; 13(7): 673-683
Published online Jul 15, 2021. doi: 10.4251/wjgo.v13.i7.673
Neoantigen vaccine: An emerging immunotherapy for hepatocellular carcinoma
Pu Chen, Qiong-Xuan Fang, Dong-Bo Chen, Hong-Song Chen
Pu Chen, Qiong-Xuan Fang, Dong-Bo Chen, Hong-Song Chen, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, Beijing 100044, China
Author contributions: Chen P, Fang QX, and Chen DB contributed equally to this work; Chen P and Fang QX wrote the paper; Chen DB collected and analyzed the data; Chen HS designed the study.
Supported by National Key Sci-Tech Special Project of China, No. 2018ZX10302207.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Hong-Song Chen, PhD, Senior Scientist, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing 100044, China.
Received: February 20, 2021
Peer-review started: February 20, 2021
First decision: March 29, 2021
Revised: April 6, 2021
Accepted: June 17, 2021
Article in press: June 17, 2021
Published online: July 15, 2021

Tumor-specific neoantigens, which are expressed on tumor cells, can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression. Among tumor immunotherapies, neoantigen vaccines are in early human clinical trials and have demonstrated substantial efficiency. Compared with more neoantigens in melanoma, the paucity and inefficient identification of effective neoantigens in hepatocellular carcinoma (HCC) remain enormous challenges in effectively treating this malignancy. In this review, we highlight the current development of HCC neoantigens in its generation, screening, and identification. We also discuss the possibility that there are more effective neoantigens in hepatitis B virus (HBV)-related HCC than in non-HBV-related HCC. In addition, since HCC is an immunosuppressive tumor, strategies that reverse immunosuppression and enhance the immune response should be considered for the practical exploitation of HCC neoantigens. In summary, this review offers some strategies to solve existing problems in HCC neoantigen research and provide further insights for immunotherapy.

Keywords: Hepatocellular carcinoma, Neoantigen, Hepatitis B virus, Screening and identification, Immunosuppression, Immunotherapy

Core Tip: In previous studies of tumor immunotherapy strategies targeting neoantigens, the unique events generating the neoantigens in each tumor have not been well studied. In this paper, we analyze the generation events of hepatocellular carcinoma (HCC) neoantigens. We also provide some methods for screening and identifying HCC neoantigens and clinical strategies for exploiting HCC neoantigens.