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World J Hepatol. Jan 27, 2022; 14(1): 140-157
Published online Jan 27, 2022. doi: 10.4254/wjh.v14.i1.140
Targets of immunotherapy for hepatocellular carcinoma: An update
Vikrant Rai, Sandeep Mukherjee
Vikrant Rai, Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
Sandeep Mukherjee, Department of Medicine, Creighton University School of Medicine, Omaha, NE 68124, United States
Author contributions: Rai V and Mukherjee S performed the literature review; Rai V wrote the manuscript; Mukherjee S edited and revised the manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interests.
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: Sandeep Mukherjee, FRCP (C), MD, Full Professor, Department of Medicine, Creighton University School of Medicine, Suite 401 Education Building, 7710 Mercy Road, Omaha, NE 68124, United States.
Received: April 7, 2021
Peer-review started: April 7, 2021
First decision: July 6, 2021
Revised: July 20, 2021
Accepted: December 25, 2021
Article in press: December 25, 2021
Published online: January 27, 2022

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.

Keywords: Hepatocellular carcinoma, Immunotherapy, Immune checkpoint inhibitors, Adoptive cell therapy, Oncolytic vaccines, Combination therapy

Core Tip: A significant proportion of patients with hepatocellular carcinoma (HCC) present with advanced disease and therapeutic strategies for such patients are limited. The tumor microenvironment mediating immune response suppression, immune tolerance, and evasion further complicate the treatment in advanced HCC. The involvement of immune response in the pathogenesis of HCC makes immunotherapy an attractive approach for the treatment of advanced HCC. Further, the recent research with beneficial results with immune checkpoint inhibition, adoptive cell transfer therapy, tumor vaccines, and combinational therapies to boost the immune response of the tumor are in development and have been discussed here.