2. Academic Validation
  3. Bifidobacterium boosts anti-PD-1 effectiveness through JAK pathway in hepatocellular carcinoma

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

Affiliations

  • 1 Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. ranhuo863@163.com.
  • 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. xiaozhenzhou250272@fjmu.edu.cn.
  • 9 Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. yanc99@sina.com.
  • # 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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