The CD4+ T-Cell Response of Melanoma Patients to a MAGE-A3 Peptide Vaccine Involves Potential Regulatory T Cells

作者: Violaine François , Sabrina Ottaviani , Nicolina Renkvist , Julie Stockis , Gerold Schuler

DOI: 10.1158/0008-5472.CAN-08-3726

关键词:

摘要: Melanoma patients were injected with various vaccines containing a MAGE-A3 peptide presented by HLA-DP4. Anti-MAGE-A3.DP4 T cells not detectable in the blood before vaccination, but their frequencies after vaccination ranged from 2 x 10(-6) to 10(-3) among CD4(+) lymphocytes of patients. The that stained ex vivo HLA-DP4 tetramers folded selected flow cytometry and amplified under clonal conditions. About 5% T-cell clones recognized MAGE-A3.DP4 antigen had CD25(+) phenotype resting state. These high capacity suppress proliferation another clone stimulation vitro. Most them FOXP3 expression state an unmethylated intron 1. They produced active transforming growth factor-beta none cytokines IFN-gamma, interleukin-2 (IL-2), IL-4, IL-5, IL-10. 20% CD25(-) significant lower suppressive activity. populations contained expressed state, demethylation was observed. We conclude can produce may exert regulatory function vivo.

参考文章(48)
Craig L. Bennett, Jacinda Christie, Fred Ramsdell, Mary E. Brunkow, Polly J. Ferguson, Luke Whitesell, Thaddeus E. Kelly, Frank T. Saulsbury, Phillip F. Chance, Hans D. Ochs, The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genetics. ,vol. 27, pp. 20- 21 ,(2001) , 10.1038/83713
Robert S. Wildin, Fred Ramsdell, Jane Peake, Francesca Faravelli, Jean-Laurent Casanova, Neil Buist, Ephrat Levy-Lahad, Massimo Mazzella, Olivier Goulet, Lucia Perroni, Franca Dagna Bricarelli, Geoffrey Byrne, Mark McEuen, Sean Proll, Mark Appleby, Mary E. Brunkow, X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nature Genetics. ,vol. 27, pp. 18- 20 ,(2001) , 10.1038/83707
Helen Y. Wang, Guangyong Peng, Zhong Guo, Ethan M. Shevach, Rong-Fu Wang, Recognition of a New ARTC1 Peptide Ligand Uniquely Expressed in Tumor Cells by Antigen-Specific CD4+ Regulatory T Cells Journal of Immunology. ,vol. 174, pp. 2661- 2670 ,(2005) , 10.4049/JIMMUNOL.174.5.2661
Djordje Atanackovic, Nasser K. Altorki, Elisabeth Stockert, Barbara Williamson, Achim A. Jungbluth, Erika Ritter, Darren Santiago, Cathy A. Ferrara, Mitsutoshi Matsuo, Annamalai Selvakumar, Bo Dupont, Yao-Tseng Chen, Eric W. Hoffman, Gerd Ritter, Lloyd J. Old, Sacha Gnjatic, Vaccine-Induced CD4+ T Cell Responses to MAGE-3 Protein in Lung Cancer Patients Journal of Immunology. ,vol. 172, pp. 3289- 3296 ,(2004) , 10.4049/JIMMUNOL.172.5.3289
Clare Baecher-Allan, Julia A. Brown, Gordon J. Freeman, David A. Hafler, CD4+CD25high Regulatory Cells in Human Peripheral Blood Journal of Immunology. ,vol. 167, pp. 1245- 1253 ,(2001) , 10.4049/JIMMUNOL.167.3.1245
Shimon Sakaguchi, Noriko Sakaguchi, Misako Itoh, Masanao Asano, Masaaki Toda, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology. ,vol. 155, pp. 1151- 1164 ,(1995)
Mary E. Brunkow, Eric W. Jeffery, Kathryn A. Hjerrild, Bryan Paeper, Lisa B. Clark, Sue-Ann Yasayko, J. Erby Wilkinson, David Galas, Steven F. Ziegler, Fred Ramsdell, Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nature Genetics. ,vol. 27, pp. 68- 73 ,(2001) , 10.1038/83784
W. H. Kruit, S. Suciu, B. Dreno, V. Chiarion-Sileni, L. Mortier, C. Robert, M. Maio, V. G. Brichard, F. Lehmann, U. Keilholz, Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: A randomized open-label phase II study of the EORTC Melanoma Group (16032- 18031) Journal of Clinical Oncology. ,vol. 26, pp. 9065- 9065 ,(2008) , 10.1200/JCO.2008.26.15_SUPPL.9065
Yi Zhang, Pascal Chaux, Vincent Stroobant, Alexander MM Eggermont, Jurgen Corthals, Bernard Maillère, Kris Thielemans, Marie Marchand, Thierry Boon, Pierre van der Bruggen, None, A MAGE-3 peptide presented by HLA-DR1 to CD4(+) T cells that were isolated from a melanoma patient vaccinated with a MAGE-3 protein Journal of Immunology. ,vol. 171, pp. 219- 225 ,(2003) , 10.4049/JIMMUNOL.171.1.219
D. Atanackovic, N. K. Altorki, Y. Cao, E. Ritter, C. A. Ferrara, G. Ritter, E. W. Hoffman, C. Bokemeyer, L. J. Old, S. Gnjatic, Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 1650- 1655 ,(2008) , 10.1073/PNAS.0707140104