title: Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient.
abstract: Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells.
  
  
  
  T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy.
  
  
  
  We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy.
  
  
  
  Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in two ways, by restoring the responsiveness of T cells by increasing the frequency and activation in peripheral blood of tumor specific T cells present in the tumor before therapy.
authors.affiliation: Immunology and Traslational Medicine Research Group, Graduated School in Biomedical Sciences, Department of Microbiology, Medical School, Universidad Nacional de Colombia, Carrera 30 #45-03 Building 471, office 304, Bogotá, Colombia South-America.|Immunology and Clinical Oncology Research Group (GIIOC), Fundación Salud de los Andes, Calle 44 No. 58-05, Bogotá, Colombia South-America.
authors.forename: David
authors.initials: D
authors.lastname: Bernal-Estévez
authors.affiliation: Clínica del Seno, Carrera 11 # 68-36, Bogotá, Colombia South-America.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Sánchez
authors.affiliation: Hospital Occidente de Kennedy E.S.E., Servicio de Oncología, Bogotá, Colombia South-America.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Tejada
authors.affiliation: Immunology and Traslational Medicine Research Group, Graduated School in Biomedical Sciences, Department of Microbiology, Medical School, Universidad Nacional de Colombia, Carrera 30 #45-03 Building 471, office 304, Bogotá, Colombia South-America. caparral@unal.edu.co.|Facultad de Medicina, Departamento de Microbiología, Universidad Nacional de Colombia, Carrera 30 Calle 45, Bogotá, Colombia. caparral@unal.edu.co.
authors.forename: Carlos
authors.initials: C
authors.lastname: Parra-López
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000276:immunology* / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D000068878:Trastuzumab; D017239:Paclitaxel
keywords: Breast cancer; CTLA-4; Chemotherapy; HER2/neu; T cells; TCR repertoire; Type I alpha dendritic cells