Mandlik DS, Mandlik SK, Choudhary HB. Immunotherapy for hepatocellular carcinoma: Current status and future perspectives. World J Gastroenterol 2023; 29(6): 1054-1075 [PMID: 36844141 DOI: 10.3748/wjg.v29.i6.1054]
Corresponding Author of This Article
Deepa S Mandlik, PhD, Assistant Professor, Department of Pharmacology, BVDU, Poona College of Pharmacy, Kothrud, Pune 411038, Maharashtra, India. deepa.mandlik@bharatividyapeeth.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Feb 14, 2023; 29(6): 1054-1075 Published online Feb 14, 2023. doi: 10.3748/wjg.v29.i6.1054
Immunotherapy for hepatocellular carcinoma: Current status and future perspectives
Deepa S Mandlik, Satish K Mandlik, Heena B Choudhary
Deepa S Mandlik, Heena B Choudhary, Department of Pharmacology, BVDU, Poona College of Pharmacy, Pune 411038, Maharashtra, India
Satish K Mandlik, Department of Pharmaceutics, BVDU, Poona College of Pharmacy, Pune 411038, Maharashtra, India
Author contributions: Mandlik DS, Mandlik SK, and Choudhary HB were responsible for literature research and drafting of the manuscript; All authors have read and approved the manuscript.
Conflict-of-interest statement: The authors declare 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Deepa S Mandlik, PhD, Assistant Professor, Department of Pharmacology, BVDU, Poona College of Pharmacy, Kothrud, Pune 411038, Maharashtra, India. deepa.mandlik@bharatividyapeeth.edu
Received: September 29, 2022 Peer-review started: September 29, 2022 First decision: December 12, 2022 Revised: December 23, 2022 Accepted: January 20, 2023 Article in press: January 20, 2023 Published online: February 14, 2023 Processing time: 133 Days and 16.9 Hours
Abstract
Hepatocellular carcinoma (HCC) is one of the world’s deadliest and fastest-growing tumors, with a poor prognosis. HCC develops in the context of chronic liver disease. Curative resection, surgery (liver transplantation), trans-arterial chemoembolization, radioembolization, radiofrequency ablation and chemotherapy are common treatment options for HCC, however, they will only assist a limited percentage of patients. Current treatments for advanced HCC are ineffective and aggravate the underlying liver condition. Despite promising preclinical and early-phase clinical trials for some drugs, existing systemic therapeutic methods for advanced tumor stages remain limited, underlining an unmet clinical need. In current years, cancer immunotherapy has made significant progress, opening up new treatment options for HCC. HCC, on the other hand, has a variety of causes and can affects the body’s immune system via a variety of mechanisms. With the speedy advancement of synthetic biology and genetic engineering, a range of innovative immunotherapies, such as immune checkpoint inhibitors [anti-programmed cell death-1 (PD-1), anti-cytotoxic T lymphocyte antigen-4, and anti-PD ligand 1 cell death antibodies], therapeutic cancer vaccines, engineered cytokines, and adoptive cell therapy have all been used for the treatment of advanced HCC. In this review, we summarize the present clinical and preclinical landscape of immunotherapies in HCC, critically discuss recent clinical trial outcomes, and address future perspectives in the field of liver cancer.
Core Tip: Hepatocellular carcinoma (HCC) is a multifaceted illness with multiple faces. It avoids early discovery, which provides the best chance of cure by resection/transplant, and systemic treatments are only of marginal efficacy at best, despite recent therapeutic advances. Current advances in immunotherapy and its combinations have altered the HCC treatment landscape, and clinical studies are continuing to pave the path forward. Immunotherapy increases survival rates and provides long-term cancer control in subsets of HCC patients while also minimizing side effects. Further research into immunotherapy in combination with current treatments for HCC in the early and intermediate stages may assist a greater spectrum of patients. Continued research into programmed cell death-1/ programmed cell death ligand 1, TMB, ctDNA, microsatellite stability, DNA mismatch repair, neutrophil/lymphocyte ratio, cytokines, and cellular peripheral immune response will hopefully identify the most reliable marker for selecting and sequencing systemic treatments to achieve the best outcome in HCC patients. Despite such significant treatment advances in HCC, numerous hurdles remain. The scientific community must figure out how to appropriately sequence these medicines for the best potential response, how to control toxicities, and how to develop indicators to monitor for response and relapse.
