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rdf:type |
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lifeskim:mentions |
umls-concept:C0027651,
umls-concept:C0030956,
umls-concept:C0039194,
umls-concept:C0042196,
umls-concept:C0086418,
umls-concept:C0278883,
umls-concept:C0805527,
umls-concept:C1274040,
umls-concept:C1332714,
umls-concept:C1416467,
umls-concept:C1423842
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pubmed:issue |
20
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pubmed:dateCreated |
2009-10-16
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/FOXP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-DQ Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/MART-1 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/MLANA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BaitschLukasL,
pubmed-author:BioleyGillesG,
pubmed-author:DerréLaurentL,
pubmed-author:DojcinovicDanijelD,
pubmed-author:JandusCamillaC,
pubmed-author:KwokWilliam WWW,
pubmed-author:LuescherImmanuel FIF,
pubmed-author:RomeroPedroP,
pubmed-author:RuferNathalieN,
pubmed-author:SpeiserDaniel EDE,
pubmed-author:TiercyJean-MarieJM,
pubmed-author:WieckowskiSébastienS
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8085-93
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19808957-Adult,
pubmed-meshheading:19808957-Aged,
pubmed-meshheading:19808957-Antigens, Neoplasm,
pubmed-meshheading:19808957-CD4-Positive T-Lymphocytes,
pubmed-meshheading:19808957-Cancer Vaccines,
pubmed-meshheading:19808957-Case-Control Studies,
pubmed-meshheading:19808957-Female,
pubmed-meshheading:19808957-Forkhead Transcription Factors,
pubmed-meshheading:19808957-HLA-A2 Antigen,
pubmed-meshheading:19808957-HLA-DQ Antigens,
pubmed-meshheading:19808957-Humans,
pubmed-meshheading:19808957-Immunotherapy,
pubmed-meshheading:19808957-MART-1 Antigen,
pubmed-meshheading:19808957-Male,
pubmed-meshheading:19808957-Melanoma,
pubmed-meshheading:19808957-Middle Aged,
pubmed-meshheading:19808957-Neoplasm Proteins,
pubmed-meshheading:19808957-Peptide Fragments,
pubmed-meshheading:19808957-Receptors, Antigen, T-Cell,
pubmed-meshheading:19808957-Th1 Cells,
pubmed-meshheading:19808957-Vaccination
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pubmed:year |
2009
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pubmed:articleTitle |
Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
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pubmed:affiliation |
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Ltd, Lausanne Branch, Hôpital Orthopédique, Lausanne, Switzerland.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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