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Article Dans Une Revue Cancer Cell Année : 2023

Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation

Bodu Liu
D.L. Spector
  • Fonction : Auteur
Sidse Ehmsen
  • Fonction : Auteur
Mikkel Green Terp
  • Fonction : Auteur
M. Egeblad
  • Fonction : Auteur

Résumé

Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, which in turn triggers NET formation. Two NET-associated proteins are required to induce chemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase 9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancer cells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance. Our work demonstrates that NETs regulate the activities of neighboring cells by trapping and activating cytokines and suggests that chemoresistance in the metastatic setting can be reduced or prevented by targeting the IL-1β-NET-TGF-β axis.
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Dates et versions

hal-04122824 , version 1 (08-06-2023)

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Citer

Alexandra Mousset, E. Lecorgne, Isabelle Bourget, Pascal Lopez, K. Jenovai, et al.. Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation. Cancer Cell, 2023, 41 (4), pp.757-775.e10. ⟨10.1016/j.ccell.2023.03.008⟩. ⟨hal-04122824⟩
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