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World J Gastrointest Oncol. Jan 15, 2022; 14(1): 163-180
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.163
Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons
Yi Luo, Fei Teng, Hong Fu, Guo-Shan Ding
Yi Luo, Fei Teng, Hong Fu, Guo-Shan Ding, Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Author contributions: Luo Y and Teng F contributed to the conception and design of the study; Luo Y performed the literature review, data analysis, and manuscript drafting; Teng F made critical revisions and was responsible for the final manuscript; Fu H participated in data analysis; Ding GS was the supervisor and participated in the manuscript editing.
Supported by National Natural Science Foundation of China, No. 81702923 and No. 81871262.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to report.
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: Fei Teng, MD, PhD, Attending Doctor, Surgeon, Surgical Oncologist, Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China. tengfei@smmu.edu.cn
Received: March 22, 2021
Peer-review started: March 22, 2021
First decision: June 16, 2021
Revised: June 30, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: January 15, 2022
Processing time: 294 Days and 9.8 Hours
Abstract

Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients. In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.

Keywords: Hepatocellular carcinoma; Liver transplantation; Immunotherapy; Immune checkpoint inhibitors; Adoptive cell transfer; Immunosuppressant

Core Tip: This review addresses revolutionized immunotherapy for hepatocellular carcinoma (HCC) in liver transplantation (LT), from downstaging or bridging management in the pretransplant setting to adjuvant or salvage strategy in the posttransplant setting. Considering that the benefit of the antitumor response outweighs the incremental risk of rejection, it is worthwhile to take immunotherapy into account as the salvage option when HCC recurs after LT. More prospective studies are required to provide direct evidence regarding immunosuppressant adjustment, biomarkers for response and the optimal selection of immunotherapy as well as patients.