Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Aug 15, 2016; 7(3): 242-255
Published online Aug 15, 2016. doi: 10.4291/wjgp.v7.i3.242
Immunobiology of hepatocarcinogenesis: Ways to go or almost there?
Pavan Patel, Steven E Schutzer, Nikolaos Pyrsopoulos
Pavan Patel, Steven E Schutzer, Department of Medicine, Rutgers-New Jersey Medical School, Newark, NJ 07101-1709, United States
Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers-New Jersey Medical School, Newark, NJ 07101-1709, United States
Author contributions: Patel P wrote the paper; Schutzer SE and Pyrsopoulos N contributed to the manuscript by providing revision and oversight of its writing.
Conflict-of-interest statement: Nikolaos Pyrsopoulos, MD: Advisory board for GILEAD, BMS, ABBVIE research for ABBVIE.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Nikolaos Pyrsopoulos, Chief, Division of Gastroenterology and Hepatology, Rutgers-New Jersey Medical School, 185 South Orange Avenue, MSB H538, Newark, NJ 07101-1709, United States.
Telephone: +1-973-9725252 Fax: +1-973-9723144
Received: April 26, 2016
Peer-review started: April 28, 2016
First decision: June 16, 2016
Revised: July 1, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: August 15, 2016

Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis. Though treatment modalities are available, mortality from this cancer remains high. Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival. Immunotherapy, with modern pharmacologic developments, is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation. This review will discuss current concepts of immunobiology in hepatocarcinogenesis along with current treatment modalities employing immunotherapy. The tumor microenvironment along with a variety of immune cells coexists and interplays to lead to tumorigenesis. Tumor infiltrating lymphocytes including CD8+ T cells, CD4+ T cells along with regulatory T cells, tumor associated macrophages, tumor associated neutrophils, myeloid derived suppressor cells, and natural killer cells interact to actively provide anti-tumor or pro-tumor effects. Furthermore, oncogenic pathways such as Raf/mitogen-activated protein kinase/extracellular-signal-regulated kinase pathway, phosphatidyl-3-kinase/AKT/mammalian target or rapamycin, Wnt/β-catenin, nuclear factor-κB and signal transducers and activators of transcription 3 may lead to activation and proliferation of tumor cells and are also considered cornerstones in tumorigenesis. Immunotherapy directed at this complex milieu of cells has been showned to be successful in cancer treatment. The use of vaccines, adoptive cell therapy and immune checkpoint inhibitor modulation are current options for therapy. Further translational research will shed light to concepts such as anti-tumor immunity which can add another alternative in the therapeutic armamentarium.

Keywords: Hepatocarcinogenesis, Adoptive cell therapy, Tumorigenesis, Hepatocellular carcinoma, Immunology, Tumorigenesis, Immunotherapy, Immunobiology, Immune checkpoint inhibitors

Core tip: Hepatocellular carcinoma is on the rise and is associated with high mortality. Cancer immunology is an expanding field with promise. This review will summarize the current concepts in the immunobiology of hepatocarcinogenesis including the interplay of a variety of immune cells involved in anti-tumor and pro-tumor effects. Oncogenic pathways currently known to effect hepatocarcinogenesis will also be discussed. Finally, currently tested and developed treatment modalities employing immunotherapy will be discussed with an outlook on future therapies.