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<p>The microbiome is increasingly recognized as playing a critical role in lung cancer prevention, diagnosis, and treatment. While bacteria are essential for tumor angiogenesis, the impact of fungi on this process remains largely unexplored. In this study, we investigate effects of <i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) on lung cancer. We show that inhalation of <i>A. fumigatus</i> increases tumor burden and angiogenesis in mouse models. Interestingly, <i>A. fumigatus</i> does not directly affect the proangiogenic abilities of tumor cells or endothelial cells. Instead, <i>A. fumigatus</i> promotes the accumulation of myeloid-derived suppressor cells (MDSCs), particularly G-MDSCs, in tumor tissues. <i>A. fumigatus</i> increases VEGF-A secretion from tumor-associated MDSCs, promoting tumor angiogenesis. Furthermore, we identify solute carrier family 7 member 11 (SLC7A11) as a key player in regulating this proangiogenic function through an interaction with High Mobility Group Box 1 (HMGB1) in MDSCs. Our results shed light on the mechanisms by which <i>A. fumigatus</i> influences MDSCs to promote angiogenesis and demonstrate that commensal fungi influence host immunity and support tumor progression.</p>

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Aspergillus fumigatus promotes tumor angiogenesis via SLC7A11 on myeloid-derived suppressor cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Wei Qu,
  • Zelin Wang,
  • Tianchen Zhu,
  • Huiyue Cui,
  • Ziqian Bing,
  • Sunan Shen,
  • Yi Shen,
  • Shaorong Yu,
  • Hongqin Zhuang,
  • Tingting Wang

摘要

The microbiome is increasingly recognized as playing a critical role in lung cancer prevention, diagnosis, and treatment. While bacteria are essential for tumor angiogenesis, the impact of fungi on this process remains largely unexplored. In this study, we investigate effects of Aspergillus fumigatus (A. fumigatus) on lung cancer. We show that inhalation of A. fumigatus increases tumor burden and angiogenesis in mouse models. Interestingly, A. fumigatus does not directly affect the proangiogenic abilities of tumor cells or endothelial cells. Instead, A. fumigatus promotes the accumulation of myeloid-derived suppressor cells (MDSCs), particularly G-MDSCs, in tumor tissues. A. fumigatus increases VEGF-A secretion from tumor-associated MDSCs, promoting tumor angiogenesis. Furthermore, we identify solute carrier family 7 member 11 (SLC7A11) as a key player in regulating this proangiogenic function through an interaction with High Mobility Group Box 1 (HMGB1) in MDSCs. Our results shed light on the mechanisms by which A. fumigatus influences MDSCs to promote angiogenesis and demonstrate that commensal fungi influence host immunity and support tumor progression.