Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

BMC Cancer

Research Article

Ramiro Sánchez¹  Rafael E. Tejada²  Carlos Parra-López³  David Bernal-Estévez⁴ 

[1] Clínica del Seno, Carrera 11 # 68-36, Bogotá South-America, Colombia;Hospital Occidente de Kennedy E.S.E., Servicio de Oncología, Bogotá South-America, Colombia;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 South-America, Colombia;Facultad de Medicina, Departamento de Microbiología, Universidad Nacional de Colombia, Carrera 30 Calle 45, Bogotá, Colombia;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 South-America, Colombia;Immunology and Clinical Oncology Research Group (GIIOC), Fundación Salud de los Andes, Calle 44 No. 58-05, Bogotá South-America, Colombia;

关键词: Breast cancer;    Type I alpha dendritic cells;    T cells;    Chemotherapy;    HER2/neu;    CTLA-4;    TCR repertoire;   

DOI  :  10.1186/s12885-016-2625-2

 received in 2016-03-10, accepted in 2016-07-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundExperimental 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.MethodsT 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s). 2016