Influence of the gut microbiota on the response to immunotherapy in hepatocellular carcinoma

For hepatocellular carcinoma (HCC) patients, the clinical efficacy of immune checkpoint inhibitors (ICIs) remains limited by low response rates. The gut microbiome as a critical modulator of ICI responsiveness in HCC. We systematically analyze the relevant gut microbial signatures distinguishing programmed death 1 therapy in responders and non-responders, with particular emphasis on prognostic taxa. Microbiome-targeted interventions, encompassing antibiotic modulation, probiotic supplementation, prebiotic administration, and fecal microbiota transplantation, may synergistically enhance the efficacy of ICIs by leveraging the immunomodulatory potential of gut-derived microbial metabolites. The mechanisms governing microbiome-mediated immunotherapeutic regulation involve multifaceted interactions, particularly through microbiota-driven immunomodulation within the tumor microenvironment. We identify key translational challenges of tumor heterogeneity in microbiomes. Future research directions emphasize the need for standardized protocols, longitudinal cohort studies, and innovative preclinical models to bridge existing knowledge gaps.