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Neutrophils

Neutrophil ferroptosis causes immunosuppression

Nature Reviews Immunology volume 23, page 6 (2023)Cite this article

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Inducers of ferroptosis (a non-apoptotic form of cell death that involves the release of oxygenated lipids) have been investigated as anti-cancer agents as they can kill tumour cells in vitro and in immunodeficient mice. However, they fail to clear tumours in immunocompetent mice. Kim et al. show that pathologically activated neutrophils (PMN-MDSCs) in tumours, which have immunosuppressive activity, spontaneously die by ferroptosis. Although this reduces their number, the oxygenated lipids liberated limit the activity of T cells. Inhibition of ferroptosis in immunocompetent mice abrogates the immunosuppressive activity of PMN-MDSCs and reduces tumour progression, particularly when combined with immune checkpoint blockade, whereas ferroptosis inducers promote tumour growth. This indicates that PMN-MDSC ferroptosis may be a targetable immunosuppressive mechanism for cancer immunotherapy.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Alexandra Flemming

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  1. Alexandra Flemming
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Correspondence to Alexandra Flemming.

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Flemming, A. Neutrophil ferroptosis causes immunosuppression. Nat Rev Immunol 23, 6 (2023). https://doi.org/10.1038/s41577-022-00820-2

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