Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2.

摘要: Abstract We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, pulsed six HLA-A*0201 binding wild-type p53 derived peptides. This was used combination low-dose interleukin-2 recently published clinical Phase II trial where 26 HLA-A2+ patients progressive late-stage metastatic breast (BC) were included. Almost 1/3rd of the obtained stable disease or minor regression during treatment positive correlation to tumour over-expression p53. In present study, we performed comprehensive analysis effector stage p53-specific CD8+ T cells use Dextramer Technology multicolour FACS. Pre- post-treatment blood samples from eight BC analysed. Independent outcome phenotypic distinctly antigen experienced (CD44high, CCR-7low CD62Llow). Furthermore, fresh 18 included vaccination prospectively examined for more general associated quantitative qualitative changes cell subpopulations. found that frequency CD4+ CD25high regulatory almost doubled after only 4 weeks weekly IL-2. addition, decrease percentage CD27highCCR-7high CD4/CD8 naive measured particularly vaccination. Finally, prior immunotherapy higher both CD28 CD27 CD8 naive/early memory chemotherapy-treated patients.