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Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes

Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote tumor relapse where the immune-suppressive tumor microenvironment (TME) could be instrumental. We established a novel syngeneic graftin...

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Autores principales: Spenlé, Caroline, Loustau, Thomas, Burckel, Hélène, Riegel, Gilles, Abou Faycal, Chérine, Li, Chengbei, Yilmaz, Alev, Petti, Luciana, Steinbach, Fanny, Ahowesso, Constance, Jost, Camille, Paul, Nicodème, Carapito, Raphael, Noël, Georges, Anjuère, Fabienne, Salomé, Nathalie, Orend, Gertraud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287883/
https://www.ncbi.nlm.nih.gov/pubmed/34290694
http://dx.doi.org/10.3389/fimmu.2021.636108
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author Spenlé, Caroline
Loustau, Thomas
Burckel, Hélène
Riegel, Gilles
Abou Faycal, Chérine
Li, Chengbei
Yilmaz, Alev
Petti, Luciana
Steinbach, Fanny
Ahowesso, Constance
Jost, Camille
Paul, Nicodème
Carapito, Raphael
Noël, Georges
Anjuère, Fabienne
Salomé, Nathalie
Orend, Gertraud
author_facet Spenlé, Caroline
Loustau, Thomas
Burckel, Hélène
Riegel, Gilles
Abou Faycal, Chérine
Li, Chengbei
Yilmaz, Alev
Petti, Luciana
Steinbach, Fanny
Ahowesso, Constance
Jost, Camille
Paul, Nicodème
Carapito, Raphael
Noël, Georges
Anjuère, Fabienne
Salomé, Nathalie
Orend, Gertraud
author_sort Spenlé, Caroline
collection PubMed
description Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote tumor relapse where the immune-suppressive tumor microenvironment (TME) could be instrumental. We established a novel syngeneic grafting model from a carcinogen-induced tongue tumor, OSCC13, to address the impact of radiotherapy on OSCC. This model revealed similarities with human OSCC, recapitulating carcinogen-induced mutations found in smoking associated human tongue tumors, abundant tumor infiltrating leukocytes (TIL) and, spontaneous tumor cell dissemination to the local lymph nodes. Cultured OSCC13 cells and OSCC13-derived tongue tumors were sensitive to irradiation. At the chosen dose of 2 Gy mimicking treatment of human OSCC patients not all tumor cells were killed allowing to investigate effects on the TME. By investigating expression of the extracellular matrix molecule tenascin-C (TNC), an indicator of an immune suppressive TME, we observed high local TNC expression and TIL infiltration in the irradiated tumors. In a TNC knockout host the TME appeared less immune suppressive with a tendency towards more tumor regression than in WT conditions. Altogether, our novel syngeneic tongue OSCC grafting model, sharing important features with the human OSCC disease could be relevant for future anti-cancer targeting of OSCC by radiotherapy and other therapeutic approaches.
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spelling pubmed-82878832021-07-20 Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes Spenlé, Caroline Loustau, Thomas Burckel, Hélène Riegel, Gilles Abou Faycal, Chérine Li, Chengbei Yilmaz, Alev Petti, Luciana Steinbach, Fanny Ahowesso, Constance Jost, Camille Paul, Nicodème Carapito, Raphael Noël, Georges Anjuère, Fabienne Salomé, Nathalie Orend, Gertraud Front Immunol Immunology Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote tumor relapse where the immune-suppressive tumor microenvironment (TME) could be instrumental. We established a novel syngeneic grafting model from a carcinogen-induced tongue tumor, OSCC13, to address the impact of radiotherapy on OSCC. This model revealed similarities with human OSCC, recapitulating carcinogen-induced mutations found in smoking associated human tongue tumors, abundant tumor infiltrating leukocytes (TIL) and, spontaneous tumor cell dissemination to the local lymph nodes. Cultured OSCC13 cells and OSCC13-derived tongue tumors were sensitive to irradiation. At the chosen dose of 2 Gy mimicking treatment of human OSCC patients not all tumor cells were killed allowing to investigate effects on the TME. By investigating expression of the extracellular matrix molecule tenascin-C (TNC), an indicator of an immune suppressive TME, we observed high local TNC expression and TIL infiltration in the irradiated tumors. In a TNC knockout host the TME appeared less immune suppressive with a tendency towards more tumor regression than in WT conditions. Altogether, our novel syngeneic tongue OSCC grafting model, sharing important features with the human OSCC disease could be relevant for future anti-cancer targeting of OSCC by radiotherapy and other therapeutic approaches. Frontiers Media S.A. 2021-07-05 /pmc/articles/PMC8287883/ /pubmed/34290694 http://dx.doi.org/10.3389/fimmu.2021.636108 Text en Copyright © 2021 Spenlé, Loustau, Burckel, Riegel, Abou Faycal, Li, Yilmaz, Petti, Steinbach, Ahowesso, Jost, Paul, Carapito, Noël, Anjuère, Salomé and Orend https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Spenlé, Caroline
Loustau, Thomas
Burckel, Hélène
Riegel, Gilles
Abou Faycal, Chérine
Li, Chengbei
Yilmaz, Alev
Petti, Luciana
Steinbach, Fanny
Ahowesso, Constance
Jost, Camille
Paul, Nicodème
Carapito, Raphael
Noël, Georges
Anjuère, Fabienne
Salomé, Nathalie
Orend, Gertraud
Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title_full Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title_fullStr Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title_full_unstemmed Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title_short Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
title_sort impact of tenascin-c on radiotherapy in a novel syngeneic oral squamous cell carcinoma model with spontaneous dissemination to the lymph nodes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287883/
https://www.ncbi.nlm.nih.gov/pubmed/34290694
http://dx.doi.org/10.3389/fimmu.2021.636108
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