PMID- 36669744 OWN - NLM STAT- MEDLINE DCOM- 20230224 LR - 20230320 IS - 1569-1802 (Electronic) IS - 0945-053X (Linking) VI - 116 DP - 2023 Feb TI - Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers. PG - 1-27 LID - S0945-053X(23)00002-1 [pii] LID - 10.1016/j.matbio.2023.01.002 [doi] AB - Tracks rich in matrix and cells, as described in several cancer types, have immunosuppressive functions and separate tumor nests and stroma, yet their origin is unknown. Immunostainings of cryosections from mouse breast tumors show that these tracks are bordered by an endothelial-like basement membrane, filled with fibers of collagen adjacent to tenascin-C (TNC) and low-tension fibronectin (Fn) fibers. While present in early-stage tumors and maturing with time, tracks still form under TNC KO conditions, however, host (not tumor cell)-derived TNC is important for track maturation. Tumor infiltrating leukocytes (mostly M2 macrophages and CD8+ T cells) are retained in tracks of early-stage tumors. Following track maturation, retained tumor infiltrating leukocyte (TIL) numbers get reduced and more CD8+ TIL enter the tumor nests in the absence of TNC. As these tracks are enriched with platelets and fibrinogen and have a demarcating endothelial-like basement membrane often adjacent to endothelial cells, this suggests a role of blood vessels in the formation of these tracks. The Fn fiber tension probe FnBPA5 colocalizes with TNC and immune cells in the tracks and shows decreased binding in tracks lacking TNC. Consequently, FnBPA5 can serve as probe for tumor matrix tracks that have immune suppressive properties. CI - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Fonta, Charlotte M AU - Fonta CM AD - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland. FAU - Loustau, Thomas AU - Loustau T AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. FAU - Li, Chengbei AU - Li C AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. FAU - Poilil Surendran, Suchithra AU - Poilil Surendran S AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. FAU - Hansen, Uwe AU - Hansen U AD - Institute for Musculoskeletal Medicine (IMM), University Hospital Muenster, Muenster, Federal Republic of Germany. FAU - Murdamoothoo, Devadarssen AU - Murdamoothoo D AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Moliere, Strasbourg, Hautepierre, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. FAU - Benn, Mario C AU - Benn MC AD - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland. FAU - Velazquez-Quesada, Ines AU - Velazquez-Quesada I AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Moliere, Strasbourg, Hautepierre, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. FAU - Carapito, Raphael AU - Carapito R AD - Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France; Platform GENOMAX, INSERM UMR_S 1109, Institut thematique interdisciplinaire (ITI) de Medecine de Precision de Strasbourg, Transplantex NG, Faculte de Medecine, Federation Hospitalo-Universitaire OMICARE, LabEx TRANSPLANTEX, Strasbourg 67091, France. FAU - Orend, Gertraud AU - Orend G AD - The Tumor Microenvironment Laboratory, INSERM U1109, Hopital Civil, Institut d' Hematologie et d'Immunologie, 1 Place de l'Hopital, Strasbourg 67091, France; MN3T (The Microenvironmental Niche in Tumorigenesis and Targeted Therapy), INSERM U1109, 3 avenue Moliere, Strasbourg, Hautepierre, France; Universite Strasbourg, Strasbourg 67000, France; Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg 67000, France. Electronic address: gertraud.orend@inserm.fr. FAU - Vogel, Viola AU - Vogel V AD - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Vladimir Prelog Weg, Zurich CH-8093, Switzerland. Electronic address: viola.vogel@hest.ethz.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230118 PL - Netherlands TA - Matrix Biol JT - Matrix biology : journal of the International Society for Matrix Biology JID - 9432592 RN - 0 (Fibronectins) RN - 0 (Tenascin) SB - IM MH - Mice MH - Animals MH - *Fibronectins/metabolism MH - Endothelial Cells/metabolism MH - *Neoplasms/pathology MH - Macrophages/metabolism MH - Tenascin/metabolism MH - CD8-Positive T-Lymphocytes/metabolism MH - T-Lymphocytes/metabolism OTO - NOTNLM OT - CD8+ T cells OT - Cancer OT - Endothelial-mesenchymal transition (EndoMT) OT - Fibronectin binding peptide FnBPA5 OT - M2 macrophages OT - Tenascin-C OT - Tumor matrix tracks EDAT- 2023/01/21 06:00 MHDA- 2023/02/25 06:00 CRDT- 2023/01/20 19:26 PHST- 2022/05/11 00:00 [received] PHST- 2022/12/31 00:00 [revised] PHST- 2023/01/12 00:00 [accepted] PHST- 2023/01/21 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2023/01/20 19:26 [entrez] AID - S0945-053X(23)00002-1 [pii] AID - 10.1016/j.matbio.2023.01.002 [doi] PST - ppublish SO - Matrix Biol. 2023 Feb;116:1-27. doi: 10.1016/j.matbio.2023.01.002. Epub 2023 Jan 18.