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Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer

BACKGROUND: Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival. METHODS: We phenotyped circulating plasmacytoid dendritic cells (pDCs), mye...

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Autores principales: Kini Bailur, Jithendra, Gueckel, Brigitte, Pawelec, Graham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884426/
https://www.ncbi.nlm.nih.gov/pubmed/27234566
http://dx.doi.org/10.1186/s12967-016-0905-x
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author Kini Bailur, Jithendra
Gueckel, Brigitte
Pawelec, Graham
author_facet Kini Bailur, Jithendra
Gueckel, Brigitte
Pawelec, Graham
author_sort Kini Bailur, Jithendra
collection PubMed
description BACKGROUND: Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival. METHODS: We phenotyped circulating plasmacytoid dendritic cells (pDCs), myeloid-derived suppressor cells (MDSCs) and regulatory T-cells in relation to T-cell responses to Her-2 in vitro in 75 untreated breast cancer patients 28–87 years of age at diagnosis. RESULTS: Patients with later stage tumors had lower levels of circulating pDCs (p = 0.008). There was a positive association between 5-year survival and higher than median levels of circulating pDCs (p = 0.03). We confirmed that 5-year survival correlated with CD8+ but not CD4+ T-cell responsiveness to Her-2 peptides in this cohort of younger and older patients (p = 0.04). Including pDCs in the analysis of previously-established parameters revealed that patients who had a CD8+ T-cell response to Her-2 together with a low ratio of MDSCs:pDCs had 100 % 5-year survival. High levels of pDCs and the presence of a CD8+ T-cell response to Her-2 were independent positive survival indicators according to multivariate Cox analysis. CONCLUSIONS: Our new results suggest that circulating pDCs could be a positive prognostic indicator in breast cancer patients of all ages, together with the previously established CD8+ T-cell reactivity to Her-2 antigens in older patients only. These two prognostic indicators were independent and emphasize the important role of immunity in ensuring breast cancer patient survival, even in those not undergoing immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0905-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-48844262016-05-29 Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer Kini Bailur, Jithendra Gueckel, Brigitte Pawelec, Graham J Transl Med Research BACKGROUND: Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival. METHODS: We phenotyped circulating plasmacytoid dendritic cells (pDCs), myeloid-derived suppressor cells (MDSCs) and regulatory T-cells in relation to T-cell responses to Her-2 in vitro in 75 untreated breast cancer patients 28–87 years of age at diagnosis. RESULTS: Patients with later stage tumors had lower levels of circulating pDCs (p = 0.008). There was a positive association between 5-year survival and higher than median levels of circulating pDCs (p = 0.03). We confirmed that 5-year survival correlated with CD8+ but not CD4+ T-cell responsiveness to Her-2 peptides in this cohort of younger and older patients (p = 0.04). Including pDCs in the analysis of previously-established parameters revealed that patients who had a CD8+ T-cell response to Her-2 together with a low ratio of MDSCs:pDCs had 100 % 5-year survival. High levels of pDCs and the presence of a CD8+ T-cell response to Her-2 were independent positive survival indicators according to multivariate Cox analysis. CONCLUSIONS: Our new results suggest that circulating pDCs could be a positive prognostic indicator in breast cancer patients of all ages, together with the previously established CD8+ T-cell reactivity to Her-2 antigens in older patients only. These two prognostic indicators were independent and emphasize the important role of immunity in ensuring breast cancer patient survival, even in those not undergoing immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0905-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-28 /pmc/articles/PMC4884426/ /pubmed/27234566 http://dx.doi.org/10.1186/s12967-016-0905-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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kini Bailur, Jithendra
Gueckel, Brigitte
Pawelec, Graham
Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title_full Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title_fullStr Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title_full_unstemmed Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title_short Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
title_sort prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884426/
https://www.ncbi.nlm.nih.gov/pubmed/27234566
http://dx.doi.org/10.1186/s12967-016-0905-x
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