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Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics
Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines – the molecule...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343793/ https://www.ncbi.nlm.nih.gov/pubmed/30713794 http://dx.doi.org/10.1080/2162402X.2018.1537691 |
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author | Jabeen, Shakila Espinoza, Jaime A. Torland, Lilly Anne Zucknick, Manuela Kumar, Surendra Haakensen, Vilde D. Lüders, Torben Engebraaten, Olav Børresen-Dale, Anne-Lise Kyte, Jon Amund Gromov, Pavel Naume, Bjørn Kristensen, Vessela Gromova, Irina Tekpli, Xavier |
author_facet | Jabeen, Shakila Espinoza, Jaime A. Torland, Lilly Anne Zucknick, Manuela Kumar, Surendra Haakensen, Vilde D. Lüders, Torben Engebraaten, Olav Børresen-Dale, Anne-Lise Kyte, Jon Amund Gromov, Pavel Naume, Bjørn Kristensen, Vessela Gromova, Irina Tekpli, Xavier |
author_sort | Jabeen, Shakila |
collection | PubMed |
description | Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines – the molecules coordinating and fine-tuning immune response – are still poorly characterized. Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the levels of 27 cytokines in the serum of breast cancer patients prior to treatment. We investigated the cytokine levels in relation to clinicopathological characteristics and in perspective of the tumor infiltrating immune cells predicted from the bulk mRNA expression data. Unsupervised clustering analysis of the serum cytokine levels in the MicMa cohort identified a cluster of pro-inflammatory, pro-angiogenic, and Th2-related cytokines which was associated with poor prognosis. Notably high levels of platelet derived growth factor BB (PDGF) reflected a more aggressive tumor phenotype and larger tumor size. A significant positive correlation between serum levels of interferon gamma-induced protein 10 (IP10) and its mRNA expression at the tumor site suggested that tumor-IP10-production may outflow to the bloodstream. High IP10 serum levels were associated with a worse prognosis. Finally, we found serum levels of both PDGF and IP10 associated with enrichment scores of specific tumor infiltrating immune cells. Our study suggests that monitoring cytokine circulating levels in breast cancer could be used to characterize breast cancers and the immune composition of their microenvironment through readily available biological material. |
format | Online Article Text |
id | pubmed-6343793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-63437932019-02-01 Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics Jabeen, Shakila Espinoza, Jaime A. Torland, Lilly Anne Zucknick, Manuela Kumar, Surendra Haakensen, Vilde D. Lüders, Torben Engebraaten, Olav Børresen-Dale, Anne-Lise Kyte, Jon Amund Gromov, Pavel Naume, Bjørn Kristensen, Vessela Gromova, Irina Tekpli, Xavier Oncoimmunology Original Research Cancers elicit an immune response by modifying the microenvironment. The immune system plays a pivotal role in cancer recognition and eradication. While the potential clinical value of infiltrating lymphocytes at the tumor site has been assessed in breast cancer, circulating cytokines – the molecules coordinating and fine-tuning immune response – are still poorly characterized. Using two breast cancer cohorts (MicMa, n = 131, DCTB, n = 28) and the multiplex Luminex platform, we measured the levels of 27 cytokines in the serum of breast cancer patients prior to treatment. We investigated the cytokine levels in relation to clinicopathological characteristics and in perspective of the tumor infiltrating immune cells predicted from the bulk mRNA expression data. Unsupervised clustering analysis of the serum cytokine levels in the MicMa cohort identified a cluster of pro-inflammatory, pro-angiogenic, and Th2-related cytokines which was associated with poor prognosis. Notably high levels of platelet derived growth factor BB (PDGF) reflected a more aggressive tumor phenotype and larger tumor size. A significant positive correlation between serum levels of interferon gamma-induced protein 10 (IP10) and its mRNA expression at the tumor site suggested that tumor-IP10-production may outflow to the bloodstream. High IP10 serum levels were associated with a worse prognosis. Finally, we found serum levels of both PDGF and IP10 associated with enrichment scores of specific tumor infiltrating immune cells. Our study suggests that monitoring cytokine circulating levels in breast cancer could be used to characterize breast cancers and the immune composition of their microenvironment through readily available biological material. Taylor & Francis 2018-11-05 /pmc/articles/PMC6343793/ /pubmed/30713794 http://dx.doi.org/10.1080/2162402X.2018.1537691 Text en © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Jabeen, Shakila Espinoza, Jaime A. Torland, Lilly Anne Zucknick, Manuela Kumar, Surendra Haakensen, Vilde D. Lüders, Torben Engebraaten, Olav Børresen-Dale, Anne-Lise Kyte, Jon Amund Gromov, Pavel Naume, Bjørn Kristensen, Vessela Gromova, Irina Tekpli, Xavier Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title | Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title_full | Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title_fullStr | Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title_full_unstemmed | Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title_short | Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
title_sort | noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343793/ https://www.ncbi.nlm.nih.gov/pubmed/30713794 http://dx.doi.org/10.1080/2162402X.2018.1537691 |
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