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

Alexandra Mousset, Enora Lecorgne, Isabelle Bourget, Pascal Lopez, Kitti Jenovai, Julien Cherfils-Vicini, Chloé Dominici, Géraldine Rios, Cédric Girard-Riboulleau, Bodu Liu, David L. Spector, Sidse Ehmsen, Shufang Renault, Caroline Hego, Fatima Mechta-Grigoriou, François Clément Bidard, Mikkel Green Terp, Mikala Egeblad, Cédric Gaggioli*, Jean Albrengues*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


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.

Original languageEnglish
JournalCancer Cell
Issue number4
Pages (from-to)757-775.e10
Publication statusPublished - 10. Apr 2023


  • Breast Cancer
  • chemoresistance
  • Lung Metastasis
  • neutrophil extracellular traps
  • TGFβ


Dive into the research topics of 'Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation'. Together they form a unique fingerprint.

Cite this