Macrophages restrict tumor immune infiltration by controlling collagen topography.
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 (<i>Tcf4</i>) 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 <i>TCF4</i>, <i>COL3A1</i>, and T cell and neutrophil signatures. Together, our data identify collagen network topographies as a key regulator of tumor-infiltrating immune cells.
Authors
- Sylvie Coscoy (ORCID: https://orcid.org/0000-0003-3963-3609)
- Vincent Calmettes (ORCID: https://orcid.org/0000-0001-6943-9116)
- Lívia Lacerda Mariano (ORCID: https://orcid.org/0000-0002-2749-4878)
- Hélène D. Moreau (ORCID: https://orcid.org/0000-0001-5715-6864)
- Giorgio Scita (ORCID: https://orcid.org/0000-0001-7984-1889)
- Valeria Sandoval Manríquez
- Mathilde Mathieu (ORCID: https://orcid.org/0000-0002-9304-9692)
- Perrine de Villemagne
- Franck Simon (ORCID: https://orcid.org/0000-0002-6952-0819)
- Emanuele Martini (ORCID: https://orcid.org/0000-0002-3375-7726)
- Jean‐Christophe Gelly (ORCID: https://orcid.org/0000-0001-5138-361X)
- Paolo Pierobon (ORCID: https://orcid.org/0000-0002-3014-0181)
- Christel Goudot (ORCID: https://orcid.org/0000-0001-6037-2314)
- Vincent Semetey (ORCID: https://orcid.org/0000-0001-8939-2538)
- Hervé Isambert (ORCID: https://orcid.org/0000-0001-9638-8545)
- Zoé Fusilier
- Lou Crestey
- Ana-Maria Lennon-Duménil
- Alexandra Clément (ORCID: https://orcid.org/0000-0003-2982-3070)
- Jeyani George Clément
- Florence Piastra-Facon
- Isabel Calvente
- Enola Lumineau
- Mattia Tonani
- Roude Jean-Marie
- Romane Henninger
- Johanna Ivaska
- Léa Bensaid
- Yazmina Quintana-Perez
- Eliane Piaggio
Institutions
- Centre National de la Recherche Scientifique (FR)
- Åbo Akademi University (FI)
- Inserm (FR)
- University of Turku (FI)
- Turku Centre for Computer Science (FI)
- University of Milan (IT)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- Sorbonne Université (FR)
- Sorbonne Paris Cité (FR)
- Finnish Cancer Registry (FI)
- Immunité et Cancer (FR)
- IFOM (IT)
- Institut de Recherche de Chimie Paris (FR)
- Institut Cochin (FR)
- Cancer Society of Finland (FI)
- Institut Curie (FR)
Publication Details
- Journal
- PubMed
- Published
- 2026-03-20
- DOI
- https://doi.org/10.1126/sciimmunol.adw8291
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00