Gut microbiota as predictors of immunotherapy response in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) remains a major cause of global cancer-related mortality, with limited therapeutic options for advanced disease. The advent of immune checkpoint inhibitors (ICIs) has revolutionized HCC treatment; however, only a subset of patients achieve durable responses, underscoring the urgent need for reliable biomarkers to guide precision immunotherapy. Emerging evidence highlights the gut microbiota as a determinant of immunotherapy efficacy through the gut-liver axis. Community diversity, specific microbial taxa, and functional metabolites have been associated with responses to ICIs. Mechanistically, gut microbes influence antigen presentation, T cell activation, and immune tolerance within the hepatic microenvironment. Moreover, microbiota-targeted interventions hold promise for restoring responsiveness in non-responders. This review summarizes the regulatory roles of the gut microbiota in HCC immunotherapy and discusses the potential of microbiota-based strategies as predictive and therapeutic tools. Integrating multi-omics, strain-level analysis, and high-resolution microbial profiling is crucial for realizing microbiota-informed precision immunotherapy in HCC.

Keywords

Gut microbiota / hepatocellular carcinoma / immunotherapy response / microbial regulation

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