Through various murine models and 5 R-16 S sequencing, we identified Bacteroides thetaiotaomicron (B.t) as a sensitizer for the combined treatment of Apatinib and anti-PD-1 therapy. Clinically, B.t enrichment was associated with improved neoadjuvant treatment outcomes and a favorable prognosis in HCC patients. Mechanistically, B.t produces formic acid in tumor cells, inhibits aryl hydrocarbon receptor (AhR) nuclear translocation by methylation, and suppresses downstream pathways, thereby mitigating pro-angiogenic effects and immunosuppression. The addition of formate or AhR inhibitors with combined treatment significantly enhanced therapeutic efficacy in preclinical models.

Hepatocellular carcinoma  /  Immunotherapy  /  Bacteroides thetaiotaomicron  /  AhR  /  Tyrosine kinase inhibitor  /  Tumor metabolism  /  Tumor microbiota  /  Therapeutic response