Bifidobacterium boosts anti-PD-1 effectiveness through JAK pathway in hepatocellular carcinoma

  • NPJ Precis Oncol. 2025 Jul 23;9(1):251. doi: 10.1038/s41698-025-00960-3.
Ran Huo  #  1 ,  Quan-Guo Xu  #  2 ,  Yi-Qing You  #  2 ,  Yan-Lin Chen  #  3 ,  Guang-Jian Su  2 ,  Kun-Rong Yang  2 ,  Yan-Ping Xiao  2 ,  Zhong Xue  4 ,  Yang-Jin Li  5 ,  Pei Sun  6 ,  Zhao-Lei Cui  2 ,  Ying-Ying Lin  2 ,  Jun-Ying Guo  2 ,  Hai-Yan Xu  2 ,  Zhao-Shuo Chen  4 ,  Wen-Ting Xie  7 ,  Shao-Hua Xu  4 ,  Min-Yong Chen  4 ,  Jing Wu  2 ,  Shi-Jie He  2 ,  Zhen-Zhou Xiao  8 ,  Yan Chen  9
Affiliations
  • 1. Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. [email protected].
  • 2. Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
  • 3. Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
  • 4. Department of Hepatobiliary and Pancreatic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
  • 5. Inspection and Testing Institute, Fujian Center for Disease Control and Prevention Health, Fuzhou, China.
  • 6. Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 7. Department of Ultrasound, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
  • 8. Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. [email protected].
  • 9. Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. [email protected].
  • # Contributed equally.
PMID: 40702094 DOI: 10.1038/s41698-025-00960-3
Abstract

Hepatocellular carcinoma (HCC) is a prevalent and deadly Cancer. Gut microbiota affect tumor immunity and immunotherapy efficacy, but the exact mechanisms are unclear. A study compared gut microbiota in HCC patients and healthy controls (HC) using 16S rDNA analysis and metabolomics. It found higher levels of Bifidobacterium and a positive correlation between Bifidobacterium and isobutyric acid in HC group. Animal models showed that the combination of HC fecal matter and αPD-1 treatment reduced tumor volume more effectively than the combination of HCC fecal matter and αPD-1. The combination of Bifidobacterium or isobutyrate with αPD-1 also decreased tumor size. In vitro, isobutyrate-stimulated CD8+T cells increased IFN-γ secretion, suppressed liver Cancer cells, and downregulated the JAK/STAT3 pathway. Combined treatments increased CD8+T cells and IFN-γ levels and reduced JAK/STAT3 signaling in the tumor microenvironment. This suggests that Bifidobacterium and isobutyrate can inhibit tumor growth, offering insights into gut microbiota-host interactions and potential strategies to overcome HCC immunotherapy resistance.

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