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

Resident tissue macrophages transfer selenium transporter Selenop to EMT-high tumor cells, promoting ferroptosis resistance and tumor progression in pancreatic ductal adenocarcinoma.

• Why it matters: Understanding how macrophages support tumor growth can reveal new therapeutic targets for aggressive cancers like PDAC, which have limited treatment options and poor prognosis.
• What they did: Using single-cell profiling, spatial analysis, lineage tracing, RTM depletion, and selenium tracing, the study identified RTMs' localization at the tumor border and their transfer of Selenop via LRP8-dependent uptake to tumor cells.
• The result: This transfer increases tumor-cell selenium, reduces lipid peroxidation, and shields cells from ferroptosis, with disruption of Selenop or Lrp8 decreasing EMT and tumor progression, suggesting potential intervention points.