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<p>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 <i>Bifidobacterium</i> and a positive correlation between <i>Bifidobacterium</i> 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 <i>Bifidobacterium</i> or isobutyrate with αPD-1 also decreased tumor size. In vitro, isobutyrate-stimulated CD8<sup>+</sup>T cells increased IFN-γ secretion, suppressed liver cancer cells, and downregulated the JAK/STAT3 pathway. Combined treatments increased CD8<sup>+</sup>T cells and IFN-γ levels and reduced JAK/STAT3 signaling in the tumor microenvironment. This suggests that <i>Bifidobacterium</i> and isobutyrate can inhibit tumor growth, offering insights into gut microbiota-host interactions and potential strategies to overcome HCC immunotherapy resistance.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月23日

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  • Ran Huo,
  • Quan-guo Xu,
  • Yi-qing You,
  • Yan-lin Chen,
  • Guang-jian Su,
  • Kun-rong Yang,
  • Yan-ping Xiao,
  • Zhong Xue,
  • Yang-jin Li,
  • Pei Sun,
  • Zhao-lei Cui,
  • Ying-ying Lin,
  • Jun-ying Guo,
  • Hai-yan Xu,
  • Zhao-shuo Chen,
  • Wen-ting Xie,
  • Shao-hua Xu,
  • Min-yong Chen,
  • Jing Wu,
  • Shi-jie He,
  • Zhen-zhou Xiao,
  • Yan Chen

摘要

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.