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

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_13A6AAC3E36C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
Périodique
Cancer Research
Auteur⸱e⸱s
Jandus C., Bioley G., Dojcinovic D., Derré L., Baitsch L., Wieckowski S., Rufer N., Kwok W.W., Tiercy J.M., Luescher I.F., Speiser D.E., Romero P.
ISSN
0008-5472
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
69
Numéro
20
Pages
8085-8093
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
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.
Mots-clé
ex vivo , melanoma , CD4 T cells , pMHCII multimers , regulatory T cells
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/10/2009 12:57
Dernière modification de la notice
20/08/2019 12:42
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