title: Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University Hospital Tübingen, Waldhoernlestr. 22, 72072, Tübingen, Germany. jithendra.kini@gmail.com.|Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA. jithendra.kini@gmail.com.
authors.forename: Jithendra
authors.initials: J
authors.lastname: Kini Bailur
authors.affiliation: Radiology Clinic, Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gueckel
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University Hospital Tübingen, Waldhoernlestr. 22, 72072, Tübingen, Germany.|School of Science and Technology, College of Arts and Science, Nottingham Trent University, Nottingham, UK.|Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, London, UK.|Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Her-2; Myeloid derived suppressor cells; Plasmacytoid dendritic cells; Regulatory T-cells; T-cells