en
Scientific article
Review
English

Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts

Published inCancer research, vol. 69, no. 20, p. 8085-8093
Publication date2009
Abstract

We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells. These are further enhanced when a TLR9 agonist is codelivered in the same vaccine formulation. Interestingly, the same peptide can be efficiently recognized by HLA-DQ6-restricted CD4 T cells. We used HLA-DQ6 multimers to assess the specific CD4 T-cell response in both healthy individuals and melanoma patients. We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide. Upon vaccination, the relative frequency of multimer+ CD4 T cells did not change significantly. In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide. A concomitant reduction in TCR diversity was also observed. This is the first report on direct ex vivo identification of antigen-specific FOXP3+ T cells by multimer labeling in cancer patients and on the direct assessment of the impact of peptide vaccination on immunoregulatory T cells.

Keywords
  • Adult
  • Aged
  • Antigens, Neoplasm/*immunology
  • CD4-Positive T-Lymphocytes/*immunology
  • Cancer Vaccines/therapeutic use
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors/*metabolism
  • HLA-A2 Antigen/immunology
  • HLA-DQ Antigens/immunology/metabolism
  • Humans
  • Immunotherapy
  • MART-1 Antigen
  • Male
  • Melanoma/*immunology/secondary/therapy
  • Middle Aged
  • Neoplasm Proteins/*immunology
  • Peptide Fragments/*immunology
  • Receptors, Antigen, T-Cell
  • Th1 Cells/*immunology
  • Vaccination
Citation (ISO format)
JANDUS, Camilla et al. Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts. In: Cancer research, 2009, vol. 69, n° 20, p. 8085–8093. doi: 10.1158/0008-5472.CAN-09-2226
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0008-5472
551views
0downloads

Technical informations

Creation04/23/2012 1:23:53 PM
First validation04/23/2012 1:23:53 PM
Update time03/14/2023 5:25:32 PM
Status update03/14/2023 5:25:32 PM
Last indexation02/12/2024 7:59:55 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack