Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancerReport as inadecuate




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Journal of Translational Medicine

, 14:151

Immunobiology and immunotherapy section

Abstract

BackgroundIdentifying 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.

MethodsWe 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.

ResultsPatients 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.

ConclusionsOur 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.

KeywordsBreast cancer T-cells Plasmacytoid dendritic cells Myeloid derived suppressor cells Regulatory T-cells Her-2 AbbreviationsHer-2human epidermal growth factor receptor-2

FoxP3forkhead box P3

ILinterleukin

DCsdendritic cells

MDSCmyeloid derived suppressor cell

TAAstumor associated antigens

aTregactivated regulatory T-cells

MPmatrix protein

NPnucleoprotein

Electronic supplementary materialThe 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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Author: Jithendra Kini Bailur - Brigitte Gueckel - Graham Pawelec

Source: https://link.springer.com/







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