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<p>The interactions between cancer cells and immune cells are crucial regulatory factors in forming the immuno-suppressive microenvironment. However, the underlying regulatory mechanisms remain elusive. In this study, we analyzed hepatocellular carcinoma (HCC) single-cell sequencing of public databases to investigate cellular interactions, revealing that cathepsin E (CTSE) highly expressed cancer cells exhibited significant interactions with T cells. Moreover, lower expression of CTSE is associated with an increased intra-tumoral CD3<sup>+</sup> T cell infiltration. Mechanistically, CTSE highly expressed cancer cells upregulated the ubiquinone signaling pathway, enhancing the synthesis and release of des-γ-carboxy prothrombin (DCP), which subsequently activates reactive oxygen species (ROS) production and leads to apoptosis of Jurkat T cells. In vivo, animal experiments show that CTSE knockdown inhibited peripheral blood DCP levels and tumor growth while significantly enhancing the effectiveness of anti-PD-1 immunotherapy. Overall, our data reveal a regulatory mechanism involving CTSE-mediated DCP release and underscore the potential of CTSE knockdown in enhancing anti-PD-1 treatment.</p><p></p>

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CTSE inhibits anti-tumor T cell response by promoting des-γ-carboxy prothrombin releasing in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月4日

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  • Yejian Wan,
  • Xiaoxia Geng,
  • Qianshi Liu,
  • Shaolong Lu,
  • Yiqiang Liu,
  • Tao Wang,
  • Xingmei Zhang,
  • Na Li,
  • Dongyun Li,
  • Zhaoshen Li,
  • Junjie Liu,
  • Hong Wu,
  • Jie Chen

摘要

The interactions between cancer cells and immune cells are crucial regulatory factors in forming the immuno-suppressive microenvironment. However, the underlying regulatory mechanisms remain elusive. In this study, we analyzed hepatocellular carcinoma (HCC) single-cell sequencing of public databases to investigate cellular interactions, revealing that cathepsin E (CTSE) highly expressed cancer cells exhibited significant interactions with T cells. Moreover, lower expression of CTSE is associated with an increased intra-tumoral CD3+ T cell infiltration. Mechanistically, CTSE highly expressed cancer cells upregulated the ubiquinone signaling pathway, enhancing the synthesis and release of des-γ-carboxy prothrombin (DCP), which subsequently activates reactive oxygen species (ROS) production and leads to apoptosis of Jurkat T cells. In vivo, animal experiments show that CTSE knockdown inhibited peripheral blood DCP levels and tumor growth while significantly enhancing the effectiveness of anti-PD-1 immunotherapy. Overall, our data reveal a regulatory mechanism involving CTSE-mediated DCP release and underscore the potential of CTSE knockdown in enhancing anti-PD-1 treatment.