title: 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.
abstract: We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed a comprehensive analysis of the effector stage of the p53-specific CD8+ T cells by the use of Dextramer Technology and multicolour FACS. Pre- and post-treatment blood samples from eight BC patients were analysed. Independent of clinical outcome p53-specific T cells were phenotypic distinctly antigen experienced (CD44high, CCR-7low and CD62Llow). Furthermore, fresh blood from 18 cancer patients included in the vaccination trial were prospectively examined for more general treatment associated quantitative and qualitative changes in T cell subpopulations. We found that the frequency of CD4+ CD25high regulatory T cells was almost doubled after only 4 weeks of weekly vaccination and low-dose IL-2. In addition, a decrease in the percentage of CD27highCCR-7high CD4/CD8 naïve T cells was measured particularly in patients with progressive disease during vaccination. Finally, prior to immunotherapy a higher percentage of both CD28 and CD27 positive CD8naïve/early effector memory T cells were present in chemotherapy-treated patients.
authors.affiliation: Department of Oncology, Center for Cancer Immune Therapy, Copenhagen University Hospital at Herlev, Denmark. inge.m.svane@dadlnet.dk
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.forename: Anders E
authors.initials: AE
authors.lastname: Pedersen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nikolajsen
authors.forename: Mai-Britt
authors.initials: MB
authors.lastname: Zocca
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007376:Interleukin-2; D016159:Tumor Suppressor Protein p53