Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts
| Autor: | Jandus, Camilla, Bioley, Gilles, Dojcinovic, Danijel, Derre, Laurent, Baitsch, Lukas, Wieckowski, Sébastien, Rufer, Nathalie, Kwok, William W., Tiercy, Jean-Marie, Luescher, Immanuel F., Speiser, Daniel Ernest, Romero, Pedro |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
ddc:616
Adult Male Antigens Neoplasm/*immunology Neoplasm Proteins/*immunology Vaccination Receptors Antigen T-Cell Middle Aged Peptide Fragments/*immunology Forkhead Transcription Factors/*metabolism Cancer Vaccines/therapeutic use MART-1 Antigen Th1 Cells/*immunology Melanoma/*immunology/secondary/therapy CD4-Positive T-Lymphocytes/*immunology Case-Control Studies HLA-DQ Antigens/immunology/metabolism Humans Female Immunotherapy HLA-A2 Antigen/immunology Aged |
| Zdroj: | Cancer Research, Vol. 69, No 20 (2009) pp. 8085-8093 |
| ISSN: | 0008-5472 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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