The Liver Microbiome in Hepatocellular Carcinoma: From Intratumoral Microbial Ecology to Immunotherapy Response

Hepatocellular carcinoma (HCC) represents one of the most lethal malignancies worldwide and commonly develops in the setting of chronic liver injury, inflammation, fibrosis, cirrhosis, and profound immune remodeling. Although immune checkpoint inhibitors and combination immunotherapy have reshaped the therapeutic landscape of advanced HCC, only a subset of patients achieve durable clinical benefit. The biological determinants of immunotherapy response and resistance remain incompletely understood, particularly within the complex hepatic tumor microenvironment.Recent studies have expanded the traditional concept of the gut-liver axis by suggesting that microbial communities may not only influence HCC through intestinal dysbiosis, microbial metabolites, bile acid signaling, and systemic inflammation, but may also be present within tumor and peritumoral liver tissues. The intratumoral and hepatic microbiome may interact with cancer cells, stromal components, immune infiltrates, and metabolic pathways, thereby shaping tumor progression, immune surveillance, therapeutic sensitivity, and clinical outcomes. These findings raise important questions regarding the origin, composition, spatial distribution, and functional consequences of microbial signatures in HCC.This Research Topic aims to provide a focused platform for studies investigating the liver microbiome in hepatocellular carcinoma, with particular emphasis on intratumoral microbial ecology, the hepatic immune microenvironment, and immunotherapy response. By integrating microbiome profiling, spatial biology, multi-omics analysis, mechanistic studies, and clinical translational research, this collection seeks to clarify how microbial communities contribute to HCC development, progression, immune escape, and treatment resistance. A deeper understanding of these interactions may support the development of microbiome-based biomarkers and therapeutic strategies to improve risk stratification, patient selection, and personalized treatment for HCC.We welcome Original Research, Reviews, Mini-Reviews, Perspectives, Clinical Studies, and Methodological articles addressing the scope and boundaries of this Research Topic, including but not limited to the following themes:1. Composition, diversity, and spatial organization of intratumoral, peritumoral, and liver-associated microbiota in hepatocellular carcinoma.2. Functional mechanisms linking hepatic or intratumoral microbial communities with hepatocarcinogenesis, tumor progression, immune escape, and the tumor microenvironment.3. Interactions among the gut microbiome, liver microbiome, bile acid metabolism, microbial metabolites, and HCC-associated immune regulation.4. The influence of gut and liver microbiota on response, resistance, and toxicity in immune checkpoint inhibitor-based therapies for HCC.5. Multi-omics and spatial omics approaches integrating metagenomics, metabolomics, single-cell sequencing, spatial transcriptomics, immune profiling, and contamination-aware microbial validation to identify microbiome-based biomarkers for HCC diagnosis, prognosis, recurrence prediction, and therapeutic response.All submissions should place the microbiome at the center of the study and include a substantive microbial component, such as microbial characterization, host–microbe mechanistic work, or clinical cohorts with microbiome data. Manuscripts on HCC immunotherapy or the tumor immune microenvironment that do not incorporate a microbiome dimension fall outside the scope of this collection. Topic editors: Ze Xiang, Jian Wu Source: https://www.frontiersin.org/research-topics/83639/the-liver-microbiome-in-hepatocellular-carcinoma-from-intratumoral-microbial-ecology-to-immunotherapy-response