Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2021; 13(9): 1132-1143
Published online Sep 15, 2021. doi: 10.4251/wjgo.v13.i9.1132
Immune aspects of hepatocellular carcinoma: From immune markers for early detection to immunotherapy
Ângelo Z Mattos, Jose D Debes, Andre Boonstra, Arndt Vogel, Angelo A Mattos
Ângelo Z Mattos, Angelo A Mattos, Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
Ângelo Z Mattos, Angelo A Mattos, Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
Jose D Debes, Department of Medicine, Division of Gastroenterology and Infectious Diseases, University of Minnesota, Minneapolis, MN 55812, United States
Jose D Debes, Andre Boonstra, Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam NL-3015, The Netherlands
Arndt Vogel, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, Germany
Author contributions: All authors contributed to this paper with conception of the manuscript, literature review and analysis, drafting and critical revision of the manuscript, and approval of the final version of the paper.
Supported by European-Latin American ESCALON consortium, funded by the EU Horizon 2020 Program, No. 825510; and Robert Wood Johnson Foundation, Harold Amos Medical Faculty Development Program (to Debes JD).
Conflict-of-interest statement: There are no conflicts of interest.
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: Ângelo Z Mattos, MD, MSc, PhD, Professor, Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, 245, Sarmento Leite St., Porto Alegre 90050-170, Brazil.
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: April 19, 2021
Revised: May 2, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: September 15, 2021

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide. Most HCCs develop in an inflammatory microenvironment, and mounting evidence emphasizes the importance of immune aspects in hepatocarcinogenesis. In normal physiology, both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells, thus preventing the development of liver cancer. However, in the setting of impaired natural killer cells and exhaustion of T cells, HCC can develop. The immunogenic features of HCC have relevant clinical implications. There is a large number of immune markers currently being studied for the early detection of liver cancer, which would be critical in order to improve surveillance programs. Moreover, novel immunotherapies have recently been proven to be effective, and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced HCC. It is expected that in the near future different subgroups of patients will benefit from specific immunotherapy. The better we understand the immune aspects of HCC, the greater the benefit to patients through surveillance aiming for early detection of liver cancer, which allows for curative treatments, and, in cases of advanced disease, through the selection of the best possible therapy for each individual.

Keywords: Hepatocellular carcinoma, Immunology, Hepatocarcinogenesis, Surveillance, Biomarker, Immunotherapy

Core Tip: Recent developments in the field of hepatocellular carcinoma have drawn attention to the immune aspects of this neoplasm. Understanding the immune features of hepatocarcinogenesis is instrumental in order to comprehend current advances in immune markers and immunotherapy. Intensifying research on immune markers may improve surveillance and allow for precision medicine. Immunotherapy is already first-line treatment for advanced hepatocellular carcinoma.