The role of AXL in cancer and fibrosis
Sturla Magnus Grøndal completed his PhD October 14, 2024 at the University of Bergen with his doctoral work "Mechanisms of Immune Dysregulation through AXL Receptor Tyrosine Kinase Signaling in Cancer and Fibrotic Diseases".
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The protein AXL is linked to the development of cancer as well as fibrosis and is upregulated in inflammation, where it promotes disease by altering the functions of immune cells.
In this PhD work, Grøndal has investigated how blocking of AXL can prevent development of cancer and fibrosis. The team found that AXL blocking improved the efficacy of immunotherapy in a mouse model of breast cancer and reduced fibrosis in mouse models of liver and kidney fibrosis. A consistent finding across the three studies was that AXL blockade resulted in a marked reduction of monocyte-derived macrophages that correlated with disease improvement. To their surprise, they also found that plasmacytoid dendritic cells (pDCs) showed a clear reduction in the breast cancer and liver fibrosis model. In the breast cancer model, a strong correlation was observed between tumor-associated pDCs, conventional DCs, and regulatory T-cells. AXL blockade reduced fibrosis in both the liver and kidney models.
These findings may suggest that AXL blockage can be used as therapeutic treatment in diseases driven by pDCs. Overall, these results suggest that AXL signaling leads to dysfunction in myeloid cells in cancer and fibrotic diseases and supports the use of AXL blockade as a therapeutic treatment.
About Grøndal
Sturla Magnus Grøndal has a bachelor's degree in nanotechnology and a master's degree in nanoscience from the University of Bergen. He embarked on his PhD in the summer of 2020 at the Department of Biomedicine/CCBIO with Professor James B. Lorens as supervisor and Professor Silke Appel as co-supervisor.
