Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients
| Autor: | Davide Soldini, Lotta von Boehmer, Alexander Knuth, Natko Nuber, Holger Moch, Claudia Matter, Jean-Marie Tiercy, Reinhard Dummer, Alessandra Curioni-Fontecedro, Maries van den Broek |
|---|---|
| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cellular immunity medicine.medical_treatment Neoplasm Proteins/genetics/*metabolism 610 Medicine & health T-Lymphocytes Regulatory/immunology In Vitro Techniques Biology Cancer Vaccines T-Lymphocytes Regulatory Epitope Epitopes Antigen Antigens Neoplasm 10049 Institute of Pathology and Molecular Pathology Cancer Vaccines/immunology Cell Line Tumor medicine Humans Amino Acid Sequence Epitopes/genetics Melanoma/genetics/*immunology/secondary/therapy Melanoma ddc:616 1000 Multidisciplinary Multidisciplinary 10177 Dermatology Clinic Cancer Immunotherapy Biological Sciences Antigens Neoplasm/genetics/*metabolism medicine.disease Neoplasm Proteins 10032 Clinic for Oncology and Hematology Cancer cell Immunology CD4-Positive T-Lymphocytes/immunology biology.protein Antibody Immunologic Memory Epitope Mapping |
| Zdroj: | Proceedings of the National Academy of Sciences, Vol. 107, No 34 (2010) pp. 15187-15192 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1002155107 |
| Popis: | Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7 + ) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4 + T-cell responses were detected in three patients (11.5%). These CT7-specific CD4 + T-cell responses were detectable in melanoma patients’ PBMCs exclusively from preexisting CD45RA − memory CD4 + T-cell pool. Additional CT7-specific memory CD4 + T-cell responses were detected in CT7 + melanoma patients after depletion of CD4 + CD25high Treg cells showing that Treg cells impact on CT7-specific CD4 + T cells in melanoma patients. CT7-specific CD4 + T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy. |
| Databáze: | OpenAIRE |
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