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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2021; 27(22): 2994-3009
Published online Jun 14, 2021. doi: 10.3748/wjg.v27.i22.2994
Hepatocellular carcinoma in viral and autoimmune liver diseases: Role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment
Alessandro Granito, Luigi Muratori, Claudine Lalanne, Chiara Quarneti, Silvia Ferri, Marcello Guidi, Marco Lenzi, Paolo Muratori
Alessandro Granito, Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna 40138, Italy
Alessandro Granito, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
Luigi Muratori, Marco Lenzi, Division of Internal Medicine and Immunorheumatology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, University of Bologna, Bologna 40138, Italy
Luigi Muratori, Marco Lenzi, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
Claudine Lalanne, Chiara Quarneti, Silvia Ferri, Marcello Guidi, Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna 40138, Italy
Paolo Muratori, Division of Internal Medicine, Morgagni-Pierantoni Hospital, Forlì 47100, Italy
Paolo Muratori, Department of Science for the Quality of Life, University of Bologna, Bologna 40138, Italy
Author contributions: Granito A, Muratori L and Muratori P reviewed the literature and drafted the manuscript; Granito A, Muratori L, Lalanne C, Ferri S, Quarneti C and Muratori P analyzed and critically interpreted literature data; all authors were involved in acquisition of data; all authors critically reviewed the manuscript and approved the final version of this manuscript.
Conflict-of-interest statement: All the authors have no conflict of interest to declare.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alessandro Granito, MD, Assistant Professor, Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Albertoni 15, Bologna 40138, Italy. alessandro.granito@unibo.it
Received: February 4, 2021
Peer-review started: February 4, 2021
First decision: March 28, 2021
Revised: April 9, 2021
Accepted: May 7, 2021
Article in press: May 7, 2021
Published online: June 14, 2021
Processing time: 118 Days and 18.6 Hours
Core Tip

Core Tip: Hepatocellular carcinoma (HCC) is the fifth most common cancer with poor prognosis despite significant improved diagnostic and therapeutic strategies. Most of HCC occurs in cirrhotic patients, with hepatitis B and C viruses being leading causes, Recent studies showed that HCC development and progression are associated with a unique immune response profile of the liver microenvironment where CD4+CD25+ Foxp3 regulatory T-cells (Tregs) play a crucial role through their immunosuppressive role. We discuss the role of Tregs in chronic liver diseases as well as in HCC initiation and the role of immunotherapy to enhance anti-tumor immune response by blocking Treg activity.