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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
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.
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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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