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A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency

Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and I...

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Autores principales: Punt, Simone, Dronkers, Emilie A. C., Welters, Marij J. P., Goedemans, Renske, Koljenović, Senada, Bloemena, Elisabeth, Snijders, Peter J. F., Gorter, Arko, van der Burg, Sjoerd H., de Jong, Robert J. Baatenburg, Jordanova, Ekaterina S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826411/
https://www.ncbi.nlm.nih.gov/pubmed/26899388
http://dx.doi.org/10.1007/s00262-016-1805-x
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author Punt, Simone
Dronkers, Emilie A. C.
Welters, Marij J. P.
Goedemans, Renske
Koljenović, Senada
Bloemena, Elisabeth
Snijders, Peter J. F.
Gorter, Arko
van der Burg, Sjoerd H.
de Jong, Robert J. Baatenburg
Jordanova, Ekaterina S.
author_facet Punt, Simone
Dronkers, Emilie A. C.
Welters, Marij J. P.
Goedemans, Renske
Koljenović, Senada
Bloemena, Elisabeth
Snijders, Peter J. F.
Gorter, Arko
van der Burg, Sjoerd H.
de Jong, Robert J. Baatenburg
Jordanova, Ekaterina S.
author_sort Punt, Simone
collection PubMed
description Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17(+) non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17(+) non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17(+) non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17(+) non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL-17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV-positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17(+) non-T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-016-1805-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-48264112016-04-20 A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency Punt, Simone Dronkers, Emilie A. C. Welters, Marij J. P. Goedemans, Renske Koljenović, Senada Bloemena, Elisabeth Snijders, Peter J. F. Gorter, Arko van der Burg, Sjoerd H. de Jong, Robert J. Baatenburg Jordanova, Ekaterina S. Cancer Immunol Immunother Original Article Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17(+) non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17(+) non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17(+) non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17(+) non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL-17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV-positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17(+) non-T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-016-1805-x) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2016-02-22 2016 /pmc/articles/PMC4826411/ /pubmed/26899388 http://dx.doi.org/10.1007/s00262-016-1805-x Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Punt, Simone
Dronkers, Emilie A. C.
Welters, Marij J. P.
Goedemans, Renske
Koljenović, Senada
Bloemena, Elisabeth
Snijders, Peter J. F.
Gorter, Arko
van der Burg, Sjoerd H.
de Jong, Robert J. Baatenburg
Jordanova, Ekaterina S.
A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title_full A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title_fullStr A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title_full_unstemmed A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title_short A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency
title_sort beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high t cell and low il-17(+) cell frequency
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826411/
https://www.ncbi.nlm.nih.gov/pubmed/26899388
http://dx.doi.org/10.1007/s00262-016-1805-x
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