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Title

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

Authors
Jandus, Camilla
Bioley, Gilles
Dojcinovic, Danijel
Derre, Laurent
Baitsch, Lukas
Wieckowski, Sébastien
Kwok, William W.
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Published in Cancer Research. 2009, vol. 69, no. 20, p. 8085-8093
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 AdultAgedAntigens, Neoplasm/*immunologyCD4-Positive T-Lymphocytes/*immunologyCancer Vaccines/therapeutic useCase-Control StudiesFemaleForkhead Transcription Factors/*metabolismHLA-A2 Antigen/immunologyHLA-DQ Antigens/immunology/metabolismHumansImmunotherapyMART-1 AntigenMaleMelanoma/*immunology/secondary/therapyMiddle AgedNeoplasm Proteins/*immunologyPeptide Fragments/*immunologyReceptors, Antigen, T-CellTh1 Cells/*immunologyVaccination
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PMID: 19808957
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Research group Compatibilité tissulaire et transplantation clinique (562)
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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. https://archive-ouverte.unige.ch/unige:19877

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Deposited on : 2012-04-23

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