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

Background: 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.

Methods: 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 monocytederived 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.

Results: 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.

Conclusions: 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.