Spenle, Caroline ORCID: 0000-0002-6353-3109, Loustau, Thomas, Murdamoothoo, Devadarssen, Erne, William, Divonne, Stephanie Beghelli-de la Forest, Veber, Romain, Petti, Luciana, Bourdely, Pierre, Morgelin, Matthias, Brauchle, Eva-Maria, Cremel, Gerard, Randrianarisoa, Vony, Camara, Abdouramane ORCID: 0000-0003-1521-4821, Rekima, Samah, Schaub, Sebastian, Nouhen, Kelly, Imhof, Thomas, Hansen, Uwe, Paul, Nicodeme, Carapito, Raphael ORCID: 0000-0002-7036-442X, Pythoud, Nicolas, Hirschler, Aurelie, Carapito, Christine, Dumortier, Helene, Mueller, Christopher G., Koch, Manuel, Schenke-Layland, Katja ORCID: 0000-0001-8066-5157, Kon, Shigeyuki, Sudaka, Anne, Anjuere, Fabienne, Van Obberghen-Schilling, Ellen and Orend, Gertraud (2020). Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma. Cancer Immunol. Res., 8 (9). S. 1122 - 1139. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2326-6074

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Abstract

Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c(+) myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin a9b1 and binding to CCL21, tenascin-C immobilized CD11c(+) cells in the stroma. Inversion of the lymph node-to- tumor CCL21 gradient, recruitment of T regulatory cells, high expression of antiinflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Spenle, CarolineUNSPECIFIEDorcid.org/0000-0002-6353-3109UNSPECIFIED
Loustau, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murdamoothoo, DevadarssenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erne, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Divonne, Stephanie Beghelli-de la ForestUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veber, RomainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petti, LucianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bourdely, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgelin, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauchle, Eva-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cremel, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Randrianarisoa, VonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camara, AbdouramaneUNSPECIFIEDorcid.org/0000-0003-1521-4821UNSPECIFIED
Rekima, SamahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaub, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nouhen, KellyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imhof, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, NicodemeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carapito, RaphaelUNSPECIFIEDorcid.org/0000-0002-7036-442XUNSPECIFIED
Pythoud, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hirschler, AurelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carapito, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dumortier, HeleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Christopher G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenke-Layland, KatjaUNSPECIFIEDorcid.org/0000-0001-8066-5157UNSPECIFIED
Kon, ShigeyukiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sudaka, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anjuere, FabienneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Obberghen-Schilling, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orend, GertraudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-321606
DOI: 10.1158/2326-6066.CIR-20-0074
Journal or Publication Title: Cancer Immunol. Res.
Volume: 8
Number: 9
Page Range: S. 1122 - 1139
Date: 2020
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 2326-6074
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DENDRITIC CELLS; POOR-PROGNOSIS; T-CELLS; HEAD; GROWTH; IMMUNOTHERAPY; ANGIOGENESIS; METASTASIS; MIGRATION; RECURRENTMultiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32160

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