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Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer

The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68(+)/iNOS(−) and Tregs CD8(+)/FoxP3(+) in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retros...

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Autores principales: Waniczek, Dariusz, Lorenc, Zbigniew, Śnietura, Mirosław, Wesecki, Mariusz, Kopec, Agnieszka, Muc-Wierzgoń, Małgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602054/
https://www.ncbi.nlm.nih.gov/pubmed/28343267
http://dx.doi.org/10.1007/s00005-017-0463-9
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author Waniczek, Dariusz
Lorenc, Zbigniew
Śnietura, Mirosław
Wesecki, Mariusz
Kopec, Agnieszka
Muc-Wierzgoń, Małgorzata
author_facet Waniczek, Dariusz
Lorenc, Zbigniew
Śnietura, Mirosław
Wesecki, Mariusz
Kopec, Agnieszka
Muc-Wierzgoń, Małgorzata
author_sort Waniczek, Dariusz
collection PubMed
description The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68(+)/iNOS(−) and Tregs CD8(+)/FoxP3(+) in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33–3.14; p = 0.001 and RR 2.08, 95% CI 1.28–3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44–27.9; p < 0.0001 and RR 12.5, 95% CI 4.9–32.4; p < 0.0001, respectively). Infiltration of TAMs CD68(+)/iNOS(−) and Tregs CD8(+)/FoxP3(+) in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC.
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spelling pubmed-56020542017-10-04 Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer Waniczek, Dariusz Lorenc, Zbigniew Śnietura, Mirosław Wesecki, Mariusz Kopec, Agnieszka Muc-Wierzgoń, Małgorzata Arch Immunol Ther Exp (Warsz) Original Article The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68(+)/iNOS(−) and Tregs CD8(+)/FoxP3(+) in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33–3.14; p = 0.001 and RR 2.08, 95% CI 1.28–3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44–27.9; p < 0.0001 and RR 12.5, 95% CI 4.9–32.4; p < 0.0001, respectively). Infiltration of TAMs CD68(+)/iNOS(−) and Tregs CD8(+)/FoxP3(+) in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC. Springer International Publishing 2017-03-25 2017 /pmc/articles/PMC5602054/ /pubmed/28343267 http://dx.doi.org/10.1007/s00005-017-0463-9 Text en © The Author(s) 2017 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
Waniczek, Dariusz
Lorenc, Zbigniew
Śnietura, Mirosław
Wesecki, Mariusz
Kopec, Agnieszka
Muc-Wierzgoń, Małgorzata
Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title_full Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title_fullStr Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title_full_unstemmed Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title_short Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer
title_sort tumor-associated macrophages and regulatory t cells infiltration and the clinical outcome in colorectal cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602054/
https://www.ncbi.nlm.nih.gov/pubmed/28343267
http://dx.doi.org/10.1007/s00005-017-0463-9
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