HCC and Immunotherapy: The Potential Predictive Role of Gut Microbiota and Future Therapeutic Strategies

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence has demonstrated the role of the gut–liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment, leading to the activation of intracellular signaling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to HCC immunotherapy, respectively. The research was conducted through the analysis of Pubmed and Web of Science (WoS) databases for literature studies on the relationship between gut microbiota and HCC from 2015 to 2025.