Resident tissue macrophages transfer selenium transporter protein to protect pancreatic cancer from ferroptosis

Tumor-associated macrophages are key regulators of PDAC progression, comprising both resident tissue macrophages (RTMs) present before tumor onset and monocyte-derived macrophages recruited during tumor development. The roles of these two ontogenetically distinct groups of macrophages during tumor progression remain unknown.

Here, combining single-cell profiling with mouse models to trace and deplete RTMs, we found that RTMs preferentially localize at the tumor border, where they promote epithelial-mesenchymal transition (EMT) and thereby PDAC progression. Mechanistically, transfer of the selenium transporter Selenop from RTMs to mesenchymal-like tumor cells suppressed lipid oxidation and shielded these cells from ferroptosis, supporting EMT.