Macrophages restrict tumor immune infiltration by controlling collagen topography

  • Sci Immunol. 2026 Mar 20;11(117):eadw8291. doi: 10.1126/sciimmunol.adw8291.
Zoé Fusilier  1  2 ,  Alexandra Clément  1 ,  Franck Simon  3 ,  Isabel Calvente  1  3 ,  Roude Jean-Marie  1  4 ,  Mathilde Mathieu  5 ,  Vincent Calmettes  1 ,  Florence Piastra-Facon  1 ,  Yazmina Quintana-Perez  1 ,  Jeyani George Clement  1 ,  Lou Crestey  1 ,  Enola Lumineau  1 ,  Romane Henninger  1 ,  Mattia Tonani  6  7 ,  Valeria Manriquez  1 ,  Livia Lacerda Mariano  1 ,  Léa Bensaid  8 ,  Perrine de Villemagne  9 ,  Eliane Piaggio  1 ,  Vincent Semetey  10 ,  Sylvie Coscoy  3 ,  Emanuele Martini  6  7 ,  Giorgio Scita  6  7 ,  Jean-Christophe Gelly  4 ,  Johanna Ivaska  5  11  12  13  14 ,  Hervé Isambert  3 ,  Christel Goudot  1 ,  Paolo Pierobon  1  15 ,  Ana-Maria Lennon-Duménil  1 ,  Hélène D Moreau  1
Affiliations
  • 1. Institut Curie, PSL University, INSERM U932, Immunity and Cancer, Paris, France.
  • 2. Université Paris-Cité, Paris, France.
  • 3. Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Physics of Cells and Cancer, Paris, France.
  • 4. Université Paris Cité, INSERM, EFS, BIGR U1134, Team DSIMB, Paris, France.
  • 5. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
  • 6. IFOM ETS, AIRC Institute of Molecular Oncology, Milan, Italy.
  • 7. Department of Oncology and Hematology-Oncology, Università degli Studi di Milano, Milan, Italy.
  • 8. Pathologie Expérimentale PMDT, Department of Pathology (PATHEX), Institut Curie, Paris, France.
  • 9. Kaer Labs, Nantes, France.
  • 10. Chimie ParisTech, Université PSL, CNRS, Institut de Recherche de Chimie Paris, Paris, France.
  • 11. Department of Life Technologies, University of Turku, Turku, Finland.
  • 12. InFLAMES Research Flagship, University of Turku, Turku, Finland.
  • 13. Western Finnish Cancer Center (FICAN West), University of Turku, Turku, Finland.
  • 14. Foundation for the Finnish Cancer Institute, Tukholmankatu 8, Helsinki, Finland.
  • 15. Université Paris Cité, CNRS, Inserm, Institut Cochin, Paris, France.
PMID: 41860994 DOI: 10.1126/sciimmunol.adw8291
Abstract

During tumorigenesis, the extracellular matrix is extensively remodeled. Whereas the impact of such remodeling on tumor growth and invasion is well described, the consequences on immune infiltration are not well understood. Combining tissue imaging and machine learning, we show that immune cell localization in tumors can be predicted by the local topography of fibrillar collagens. Such topographies are dictated by a fibrotic pathway driven by transcription factor 4 (Tcf4) in both Cancer and stromal cells, which promotes Collagen III deposition and results in intermingled Collagen networks that favor intratumor infiltration of T cells and neutrophils. Macrophages inhibit this pathway, highlighting their key structural role in shaping the tumor extracellular matrix. Reanalysis of data from human solid tumors revealed a strong correlation between TCF4, COL3A1, and T cell and neutrophil signatures. Together, our data identify Collagen network topographies as a key regulator of tumor-infiltrating immune cells.

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