A1 Refereed original research article in a scientific journal
Macrophages restrict tumor immune infiltration by controlling collagen topography
Authors: Fusilier, Zoé; Clément, Alexandra; Simon, Franck; Calvente, Isabel; Jean-Marie, Roude; Mathieu, Mathilde; Calmettes, Vincent; Piastra-Facon, Florence; Quintana-Perez, Yazmina; Clement, Jeyani George; Crestey, Lou; Lumineau, Enola; Henninger, Romane; Tonani, Mattia; Manriquez, Valeria; Lacerda Mariano, Livia; Bensaid, Léa; De Villemagne, Perrine; Piaggio, Eliane; Semetey, Vincent; Coscoy, Sylvie; Martini, Emanuele; Scita, Giorgio; Gelly, Jean-Christophe; Ivaska, Johanna; Isambert, Hervé; Goudot, Christel; Pierobon, Paolo; Lennon-Duménil, Ana-Maria; Moreau, Hélène D.
Publication year: 2026
Journal: Science Immunology
Article number: eadw8291
Volume: 11
Issue: 117
eISSN: 2470-9468
DOI: https://doi.org/10.1126/sciimmunol.adw8291
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : No Open Access publication channel
Web address : https://www.science.org/doi/10.1126/sciimmunol.adw8291
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.
Funding information in the publication:
This work was supported by ANR-JCJC InfEx (ANR-20-CE15-0023) and ARC PJA1 NexT (ARCPJA2023070006800) to H.D.M., ERC Synergy SHAPINCELLFATE to A.-M.L.-D., the Fondation Chercher Trouver, ANR-10-IDEX-0001-02 PSL (LabEx DCBIOL), and Grand Programme PSL Devine. This work has received support under the program France 2030 launched by the French government. Z.F. was funded by ITMO Cancer. F.S. and H.I. acknowledge funding from ANR-22-PESN-0002 AI4scMed. S.C. and V.S. acknowledge funding from ANR-20-CE15-0023 FibersForCells. This work was also supported by the Finnish Cancer Institute (K. Albin Johansson Professorship), Research Council of Finland Centre of Excellence program (#346131), and ERC AdG BorderControl to J.I. Work done by G.S. is supported in part by the following grants: ERC-Synergy (grant no. 101071470), AIRC-IG (grant no. 22821), AIRC 5x1000 (#22759), and the Italian Ministry of University and Research (PRIN202223GSCIT_01/G53D23002570006/20229RM8A_001, COMBINE/G53D23007040001/P2022RH4HH002, and PNRR_ CN3RNA _SPOKE/G43C22001320007).
