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Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma
PURPOSE: In recent years the tumor microenvironment and its interaction with the tumor has emerged into research focus with increased attention to the composition of Tumor-infiltrating lymphocytes. We wanted to quantify the composition of Regulatory T cells (Tregs) and T helper 17 cells (Th17 cells)...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129928/ https://www.ncbi.nlm.nih.gov/pubmed/35763108 http://dx.doi.org/10.1007/s00432-022-04101-2 |
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author | Marchenko, Sofya Piwonski, Iris Hoffmann, Inga Sinn, Bruno Valentin Kunze, Catarina Alisa Monjé, Nanna Pohl, Jonathan Kulbe, Hagen Schmitt, Wolfgang Daniel Darb-Esfahani, Sylvia Braicu, Elena Ioana von Brünneck, Ann-Christin Sehouli, Jalid Denkert, Carsten Horst, David Jöhrens, Korinna Taube, Eliane Tabea |
author_facet | Marchenko, Sofya Piwonski, Iris Hoffmann, Inga Sinn, Bruno Valentin Kunze, Catarina Alisa Monjé, Nanna Pohl, Jonathan Kulbe, Hagen Schmitt, Wolfgang Daniel Darb-Esfahani, Sylvia Braicu, Elena Ioana von Brünneck, Ann-Christin Sehouli, Jalid Denkert, Carsten Horst, David Jöhrens, Korinna Taube, Eliane Tabea |
author_sort | Marchenko, Sofya |
collection | PubMed |
description | PURPOSE: In recent years the tumor microenvironment and its interaction with the tumor has emerged into research focus with increased attention to the composition of Tumor-infiltrating lymphocytes. We wanted to quantify the composition of Regulatory T cells (Tregs) and T helper 17 cells (Th17 cells) and their prognostic impact in high-grade serous tubo-ovarian carcinoma. METHODS: Tregs and Th17 cells were determined by immunohistochemical analysis of CD25 FoxP3 and RORγt, respectively on tissue microarrays of a cohort of 222 patients with reviewed histology and available clinical data. Expression was analyzed with Qupath for quantification and integration with clinical data enabled calculation of prognostic impact. For validation FOXP3 and RORC mRNA expression levels from 502 patients with HGSC in publicly available datasets were evaluated. RESULTS: An average percentage of 0.93 Tregs and of 0.06 Th17 cells was detected per cells in overall tissue. Optimal cut-offs were determined and higher Tregs were associated with a better overall survival in stroma (p = 0.006), tumor area (p = 0.0012) and overall tissue (p = 0.02). After accounting for well-known prognostic factors age at diagnosis, residual tumor and FIGO stage, this association remained significant for stromal Tregs with overall survival (p = 0.02). Survival analysis for Th17 cells revealed no significant association with survival rates. Moreover, lower Th17/Treg ratios had a positive impact on patient overall survival (p = 0.025 tumor, p = 0.049 stroma and p = 0.016 overall tissue). CONCLUSION: Our results outline a positive prognostic effect for higher Tregs but not for Th17 in high grade serous tubo-ovarian carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04101-2. |
format | Online Article Text |
id | pubmed-10129928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-101299282023-04-27 Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma Marchenko, Sofya Piwonski, Iris Hoffmann, Inga Sinn, Bruno Valentin Kunze, Catarina Alisa Monjé, Nanna Pohl, Jonathan Kulbe, Hagen Schmitt, Wolfgang Daniel Darb-Esfahani, Sylvia Braicu, Elena Ioana von Brünneck, Ann-Christin Sehouli, Jalid Denkert, Carsten Horst, David Jöhrens, Korinna Taube, Eliane Tabea J Cancer Res Clin Oncol Research PURPOSE: In recent years the tumor microenvironment and its interaction with the tumor has emerged into research focus with increased attention to the composition of Tumor-infiltrating lymphocytes. We wanted to quantify the composition of Regulatory T cells (Tregs) and T helper 17 cells (Th17 cells) and their prognostic impact in high-grade serous tubo-ovarian carcinoma. METHODS: Tregs and Th17 cells were determined by immunohistochemical analysis of CD25 FoxP3 and RORγt, respectively on tissue microarrays of a cohort of 222 patients with reviewed histology and available clinical data. Expression was analyzed with Qupath for quantification and integration with clinical data enabled calculation of prognostic impact. For validation FOXP3 and RORC mRNA expression levels from 502 patients with HGSC in publicly available datasets were evaluated. RESULTS: An average percentage of 0.93 Tregs and of 0.06 Th17 cells was detected per cells in overall tissue. Optimal cut-offs were determined and higher Tregs were associated with a better overall survival in stroma (p = 0.006), tumor area (p = 0.0012) and overall tissue (p = 0.02). After accounting for well-known prognostic factors age at diagnosis, residual tumor and FIGO stage, this association remained significant for stromal Tregs with overall survival (p = 0.02). Survival analysis for Th17 cells revealed no significant association with survival rates. Moreover, lower Th17/Treg ratios had a positive impact on patient overall survival (p = 0.025 tumor, p = 0.049 stroma and p = 0.016 overall tissue). CONCLUSION: Our results outline a positive prognostic effect for higher Tregs but not for Th17 in high grade serous tubo-ovarian carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04101-2. Springer Berlin Heidelberg 2022-06-28 2023 /pmc/articles/PMC10129928/ /pubmed/35763108 http://dx.doi.org/10.1007/s00432-022-04101-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Marchenko, Sofya Piwonski, Iris Hoffmann, Inga Sinn, Bruno Valentin Kunze, Catarina Alisa Monjé, Nanna Pohl, Jonathan Kulbe, Hagen Schmitt, Wolfgang Daniel Darb-Esfahani, Sylvia Braicu, Elena Ioana von Brünneck, Ann-Christin Sehouli, Jalid Denkert, Carsten Horst, David Jöhrens, Korinna Taube, Eliane Tabea Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title | Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title_full | Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title_fullStr | Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title_full_unstemmed | Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title_short | Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma |
title_sort | prognostic value of regulatory t cells and t helper 17 cells in high grade serous ovarian carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129928/ https://www.ncbi.nlm.nih.gov/pubmed/35763108 http://dx.doi.org/10.1007/s00432-022-04101-2 |
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