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Figure 1. Roles of the gut microbiota in HCC immunotherapy response. (A) Microbiota-derived SCFAs exert context-dependent effects on hepatic immunity, regulating M1 macrophage polarization, ILC3 function, and Treg differentiation; (B) Microbiota-derived BAs induce immunosuppressive reprogramming of macrophages and Kupffer cells, suppressing antitumor immunity; (C) Microbial reprogramming of IAA production impairs CD8⁺ T-cell function, contributing to immunotherapy resistance; (D) Co-stimulation of microbiota-derived riboflavin metabolites via MR1 and CpG (TLR9 agonist) activates MAIT cells, thus enhancing antitumor immune responses; (E) Microbial components and intrahepatic bacteria promote HCC cell invasion and proliferation, thereby impairing antitumor immune responses. Created in BioRender. Hu, S. (2026) https://BioRender.com/rh59ehn. HCC: Hepatocellular carcinoma; SCFA: short-chain fatty acid; ILC3: group 3 innate lymphoid cell; Treg: regulatory T cell; BA: bile acid; TCA: taurocholic acid; isoallo-LCA: isoallolithocholic acid; MP2: Marco⁺ IL-10⁺ Kupffer cells; IAA: indole-3-acetic acid; 5-OP-RU: 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil; MAIT: mucosal-associated invariant T cell; IFN-γ: interferon-γ; GZMB: granzyme B; LPS: microbial-derived lipopolysaccharide; TLR: Toll-like receptor.