Minireviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2024; 16(10): 1158-1168
Published online Oct 27, 2024. doi: 10.4254/wjh.v16.i10.1158
Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients
Wei-Hua Cao, Ya-Qin Zhang, Xin-Xin Li, Zi-Yu Zhang, Ming-Hui Li
Wei-Hua Cao, Ya-Qin Zhang, Xin-Xin Li, Zi-Yu Zhang, Ming-Hui Li, Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Ming-Hui Li, Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
Co-first authors: Wei-Hua Cao and Ya-Qin Zhang.
Author contributions: Li MH conceived the idea for the manuscript; Cao WH, Zhang YQ, and Li MH reviewed the literature and drafted the manuscript; Li XX and Zhang ZY reviewed the literature and proofread the manuscript.
Supported by The National Key Research and Development Program, No. 2022YFC2603500 and No. 2022YFC2603505; Beijing Municipal Health Commission High-Level Public Health Technical Personnel Construction Project, No. Discipline leader-03-26; The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority, No. XXZ0302; The Capital Health Research and Development of Special Public Health Project, No. 2022-1-2172; and Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support, No. XMLX 202127.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Hui Li, MD, PhD, Chief Doctor, Professor, Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, No. 8 Jingshun East Street, Chaoyang District, Beijing 100015, China. wuhm2000@sina.com
Received: June 18, 2024
Revised: August 28, 2024
Accepted: September 19, 2024
Published online: October 27, 2024
Processing time: 124 Days and 12.3 Hours
Abstract

Hepatitis B virus (HBV) infection plays an important role in the occurrence and development of hepatocellular carcinoma (HCC), and the rate of HBV infection in liver cancer patients in China is as high as 92.05%. Due to long-term exposure to chronic antigens from the gut, the liver needs to maintain a certain level of immune tolerance, both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors. Therefore, HBV infection interacts with the tumor microenvironment (TME) through a highly complex and intertwined signaling pathway, which results in a special TME in HCC. Due to changes in the TME, tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1). Interferons, as a class of immune factors with strong biological activity, can improve the TME of HBV-HCC through various pathways. In recent years, the systematic treatment of HCC has gradually come out of the dilemma. In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs, immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC. At present, immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC, and the disease characteristics of patients included in global clinical studies are different from those of Chinese patients. Therefore, whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern. This review aims to elucidate the advances of immunotherapy for HBV related HCC patients with regard to: (1) Immunotherapy based on interferons; (2) Immunotherapy based on PD-1/L1 inhibitors; (3) Immunotherapy based on CTLA4 inhibitors; (4) Adoptive cell transfer; (5) Combination immunotherapy strategy; and (6) Shortcomings of immunotherapy.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Immune checkpoint inhibitors; Peginterferon alpha; Systematic treatment

Core Tip: Hepatitis B virus (HBV) infection interacts with the tumor microenvironment (TME) through a highly complex and intertwined signaling pathway, which results in a special TME in hepatocellular carcinoma (HCC). Due to changes in the TME, tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through CTLA-4 and programmed cell death 1 (PD-1)/PD ligand 1. Interferons, as a class of immune factors with strong biological activity, can improve the TME of HBV-HCC through various pathways. Currently, the systematic treatment of HCC has gradually come out of the dilemma. In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs, immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC. Since the disease characteristics of patients included in global clinical studies are different from those of Chinese patients, whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.