Immunotherapy and liver transplantation for hepatocellular carcinoma: Current and future challenges

Abstract

Despite existing curative options like surgical removal, tissue destruction techniques, and liver transplantation for early-stage hepatocellular carcinoma (HCC), the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies. This review critically assesses the dynamic treatment panorama for HCC, focusing specifically on the burgeoning role of immunotherapy in two key contexts: early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy. It delves into the unique immunobiology of the liver and HCC, highlighting tumor-mediated immune evasion mechanisms. Analyzing the diverse immunotherapeutic approaches including checkpoint inhibitors, cytokine modulators, vaccines, oncolytic viruses, antigen-targeting antibodies, and adoptive cell therapy, this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring. Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC, current research is actively exploring the safety and effectiveness of diverse immunotherapeutic approaches through ongoing clinical trials. The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant, highlighting the need for careful patient selection, meticulous monitoring, and novel strategies to mitigate post-transplant complications. Finally, this review delves into the latest findings from the clinical research landscape and future directions in HCC management, paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.

Keywords: Hepatocellular carcinoma; Immunotherapy; Liver transplantation; Neoadjuvant and adjuvant immunotherapy; Immune checkpoint inhibitors; Vaccine therapies; Oncolytic viruses; Adoptive cell therapy; Antigen-targeting antibodies; Diagnostic biomarkers

Core Tip: Hepatocellular carcinoma is a prevalent condition nowadays. The increasing number of new cases worldwide requires intensive research and innovative curative options. Cancer immunotherapy constitutes a constantly growing field in terms of disease treatment, as well as potential tumor downstaging with an eye to liver transplantation. There are two approaches regarding immunotherapy for hepatocellular carcinoma: boosting the existing immune response and stimulating a de novo immune response.