Macrophages restrict tumor immune infiltration by controlling collagen topography.

IF 16.4 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2026-03-20 DOI:10.1126/sciimmunol.adw8291

Zoé Fusilier,Alexandra Clément,Franck Simon,Isabel Calvente,Roude Jean-Marie,Mathilde Mathieu,Vincent Calmettes,Florence Piastra-Facon,Yazmina Quintana-Perez,Jeyani George Clement,Lou Crestey,Enola Lumineau,Romane Henninger,Mattia Tonani,Valeria Manriquez,Livia Lacerda Mariano,Léa Bensaid,Perrine de Villemagne,Eliane Piaggio,Vincent Semetey,Sylvie Coscoy,Emanuele Martini,Giorgio Scita,Jean-Christophe Gelly,Johanna Ivaska,Hervé Isambert,Christel Goudot,Paolo Pierobon,Ana-Maria Lennon-Duménil,Hélène D Moreau

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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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巨噬细胞通过控制胶原地形图限制肿瘤免疫浸润。

在肿瘤发生过程中，细胞外基质被广泛重塑。尽管这种重塑对肿瘤生长和侵袭的影响已被很好地描述，但对免疫浸润的影响尚不清楚。结合组织成像和机器学习，我们发现免疫细胞在肿瘤中的定位可以通过纤维状胶原的局部地形来预测。这种地形是由癌症和基质细胞中转录因子4 （Tcf4）驱动的纤维化途径决定的，该途径促进胶原III沉积，并导致混合的胶原网络，有利于T细胞和中性粒细胞的肿瘤内浸润。巨噬细胞抑制这一途径，突出了它们在形成肿瘤细胞外基质中的关键结构作用。对人类实体肿瘤数据的重新分析显示，TCF4、COL3A1与T细胞和中性粒细胞特征之间存在很强的相关性。总之，我们的数据确定胶原网络拓扑结构是肿瘤浸润免疫细胞的关键调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.