Perforin drives ferroptosis through iron overload to boost anti-tumor immunity
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A study published in Cell on 23 October 2026 reports that perforin, a protein released by cytotoxic immune cells, can kill tumor cells through a mechanism independent of granzymes. Perforin promotes iron uptake and mitochondrial iron overload in tumor cells, triggering iron-induced mitochondrial damage and ferroptosis, a form of cell death distinct from apoptosis. This pathway connects cytotoxic immunity to iron metabolism, and the authors show it can predict which patients respond to immune checkpoint blockade. Based on these findings, they propose that iron supplementation may offer a way to strengthen anti-tumor immunity. The work is newly published; clinical testing of iron supplementation as an immunotherapy adjunct has not yet been reported.
Written by a model from the reports · updated 3 hours ago
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- cell.comPickPerforin triggers iron-induced mitochondrial damage to drive ferroptosis and anti-tumor immunity
Perforin can trigger ferroptosis by promoting iron uptake and mitochondrial iron overload, forming a tumor cell killing mechanism independent of granzymes. This pathway links cytotoxic immunity to iron metabolism and predicts patient response to immune checkpoint blockade. The authors propose that iron supplementation may be a way to enhance anti-tumor immunity.
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