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

Abstract 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.