Abstract
IntroductionBreast cancer is one of the most common cancers among women. Its incidence is increasing in many countries and a higher number of older women are now being diagnosed with the disease. Immune parameters are implicated in disease progression, and the frequencies of both myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), associated with tumour burden, have been suggested to be indicators of poor prognosis in cases of metastatic breast cancer.MethodsHere, we have assessed the frequency of peripheral Tregs and MDSCs in relation to in vitro T cell responses to Her2 antigen in 40 untreated breast cancer patients 65 to 87 years of age at diagnosis.ResultsThe five-year survival rate of patients who mounted a CD8+ T cell response to Her2 peptides and had a lower frequency of Lin−CD14+HLA-DR−MDSCs was 100% compared to only 38% in patients without Her2-reactive CD8+ T cells and with higher frequencies of MDSCs (P = 0.03). Patients who lacked a CD8 response to Her2 tended to have higher frequencies of MDSCs. Similarly, patients who lacked a CD8 response to Her2 and had higher frequencies of CD4+Foxp3+CD127lowCD25+ Tregs had only 50% survival compared to the 100% survival of patients who did mount a CD8 response and had lower frequencies of Tregs (P = 0.03). A similar trend was observed for activated (CD4+CD45RA−Foxp3hi) but not resting Tregs (CD4+CD45RA+FoxP3+). This survival advantage was observed in both metastatic and non-metastatic patients.ConclusionsOur data demonstrate a negative role of both MDSCs and Tregs in the prognosis of breast cancer patients, the mechanism of which might be through dampening favourable CD8+ T cell immune responses to tumour-associated antigens.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0541-z) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer is one of the most common cancers among women
The cells were stained with the following monoclonal antibodies: CD3-Pacific Orange (Invitrogen, Carlsbad, CA, USA), CD4-Pacific Blue, tumour necrosis factor (TNF)-fluorescein isothiocyanate (FITC), IL-2-Alexa Fluor-700, IL-5-phycoerythrin (PE) (BioLegend, San Diego, CA, USA), CD8-allophycocyaninindocyanine 7 (APC-Cy7), interferon gamma (IFN-γ)
Tumour stage and immunosuppressive subsets We showed above that CD8+ T cell responses to human epidermal growth factor receptor 2 (Her2) correlated with tumour stage and patient survival
Summary
Breast cancer is one of the most common cancers among women. Its incidence is increasing in many countries and a higher number of older women are being diagnosed with the disease. Immune parameters are implicated in disease progression, and the frequencies of both myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), associated with tumour burden, have been suggested to be indicators of poor prognosis in cases of metastatic breast cancer. For successful immunosurveillance and exploitation of such host anti-tumour reactivity in immunotherapy, it is likely important for the patient to be able to neutralize or decrease the activity of immunosuppressive cells, both T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). These have been implicated in negating anti-tumour activity in several types of cancers [11,12,13]. The frequencies and ratios of aTreg and rTreg are known to change in some diseases and can provide additional information on the likely suppressive milieu [18]
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