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

Inge Marie Svane, Anders E Pedersen, Kirsten Nikolajsen, Mai-Britt Zocca

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.

Original languageEnglish
JournalVaccine
Volume26
Issue number36
Pages (from-to)4716-24
Number of pages9
ISSN0264-410X
DOIs
Publication statusPublished - 26 Aug 2008

Keywords

  • Adjuvants, Immunologic/administration & dosage
  • Breast Neoplasms/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • CD8-Positive T-Lymphocytes/immunology
  • Cancer Vaccines/immunology
  • Dendritic Cells/immunology
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-2/administration & dosage
  • Leukocytes, Mononuclear/immunology
  • Lymphocyte Subsets/immunology
  • T-Lymphocytes, Regulatory/immunology
  • Tumor Suppressor Protein p53/immunology
  • Vaccination/methods

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