title: Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients.
abstract: Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood experience survival superior to patients without these cells. Here, we define a composite set of biomarkers that identify patients with T cell responses to tumour antigens.
  
  
  
  We assessed T cell responses following in vitro stimulation with the HER2, MUC1 and SUR tumour-associated antigens (TAA) by flow cytometry and intracellular cytokine staining in 50 breast cancer patients. We also measured HLA type, serum cytokines, tumour-infiltrating leukocytes and blood leukocyte populations.
  
  
  
  We found few correlations between TAA-reactive T cells and HLA type, serum cytokines and tumour-infiltrating leukocytes, whereas blood leukocyte phenotypes broadly correlated with TAA responses. This showed monocytes, natural killer cells, dendritic cells and T cells to be inversely associated with both CD4+ and CD8+ T cells reactive to tumour antigens. Moreover, combining multiple parameters improved the accuracy in predicting patients with TAA-responsive T cells.
  
  
  
  This study therefore defines composite immune profiles that identify patients responding to TAAs which may allow better personalisation of cancer therapies.
authors: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.
authors: Nicole
authors: N
authors: Janssen
authors: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors: Sotirios P
authors: SP
authors: Fortis
authors: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.
authors: Lisa
authors: L
authors: Speigl
authors: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors: Christoforos
authors: C
authors: Haritos
authors: Pathology Department, Saint Savas Cancer Hospital, Athens, Greece.
authors: Nectaria N
authors: NN
authors: Sotiriadou
authors: Pathology Department, Saint Savas Cancer Hospital, Athens, Greece.
authors: Michael
authors: M
authors: Sofopoulos
authors: Pathology Department, Saint Savas Cancer Hospital, Athens, Greece.
authors: Niki
authors: N
authors: Arnogiannaki
authors: Histocompatibility & Immunogenetics Lab, Hellenic Cord Blood Bank- H&I Laboratory, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Catherine
authors: C
authors: Stavropoulos-Giokas
authors: Histocompatibility & Immunogenetics Lab, Hellenic Cord Blood Bank- H&I Laboratory, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Amalia
authors: A
authors: Dinou
authors: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors: Sonia
authors: S
authors: Perez
authors: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany.|Institute of Cancer Sciences, The University of Manchester, Manchester, M20 4BX, UK.|School of Science and Technology, College of Arts and Science, Nottingham Trent University, Burton St, Nottingham, NG1 4BU, UK.|Department of Haematological Medicine, The Rayne Institute, King's College London, London, UK.
authors: Graham
authors: G
authors: Pawelec
authors: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors: Constantin N
authors: CN
authors: Baxevanis
authors: Department of Internal Medicine II, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany. mrchristophershipp@gmail.com.
authors: Christopher
authors: C
authors: Shipp
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D055261:Immunogenetic Phenomena; D016130:Immunophenotyping; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D016207:Cytokines; D006680:HLA Antigens; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Blood leukocytes; Breast cancer; HER2; MUC1; Survivin; Tumour-associated antigen