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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0905-x) contains supplementary material, which is available to authorized users.
Highlights
Identifying immune markers in blood that are informative for breast cancer patient survival would be useful for prognosis but might provide mechanistic insights into processes facilitating survival
We have previously reported that peripheral T-cell reactivity to certain tumor-associated antigens (TAAs) in melanoma correlates with a survival benefit [21, 22]
Dendritic cells (DCs), myeloid derived suppressor cell (MDSC), Tregs and tumor characteristics Neither the frequencies of total DCs nor monocytic DCs (mDCs) in the peripheral blood were found to differ between patients at tumor stage 0, 1-versus-2, 3, 4
Summary
Identifying immune markers in blood that are informative for breast cancer patient survival would be useful for prognosis but might provide mechanistic insights into processes facilitating survival. Low levels of circulating pDCs have a negative correlation with survival [14]. We have previously reported that peripheral T-cell reactivity to certain tumor-associated antigens (TAAs) in melanoma correlates with a survival benefit [21, 22]. Antigen presentation by pDCs could contribute to the induction of specific CD4+ and CD8+ T-cell responses [27, 28], but this would be contrary to the findings discussed above implying that high levels of pDCs in the tumor and low levels in the blood have a negative prognostic impact. The present study focuses on investigating the prognostic relevance of circulating antigen-presenting cells including total DCs, mDCs and pDCs separately, together with functional Her-2-reactive T-cells assayed in vitro, and an assessment of the impact of immunosuppressive cells on 5-year survival of breast cancer patients. This study goes beyond our previous work in examining pDCs but in extending the age range of the patients to include younger as well as elderly subjects
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