Analysis of T-cell responses in metastatic melanoma patients vaccinated with dendritic cells pulsed with tumor lysates |
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Authors: | Marieke?Griffioen,Martina?Borghi,Peter?I.?Schrier,Susanne?Osanto,Dirk?Schadendorf author-information" > author-information__contact u-icon-before" > mailto:d.schadendorf@dkfz.de" title=" d.schadendorf@dkfz.de" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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Affiliation: | (1) Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands;(2) Skin Cancer Unit, German Cancer Research Center and Department of Dermatology, University Hospital Mannheim, Universität Heidelberg, Theodor Kutzer Ufer 1, 68167 Mannheim, Germany |
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Abstract: | In melanoma patients, CD8+ cytotoxic T cells have been found recognizing self-proteins of which the expression is restricted to the melanocytic lineage. These melanocyte differentiation antigens are expressed in normal melanocytes as well as in 80–100% of primary and metastatic melanoma. In this report, six HLA-A*0201–subtyped metastatic melanoma patients vaccinated with dendritic cells (DCs) pulsed with autologous tumor lysates and keyhole limpet hemocyanin (KLH) were screened for the presence of CD8+ T cells specific for three HLA-A*0201–binding peptides derived from the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase. For this purpose, nonstimulated as well as in vitro peptide-stimulated peripheral blood mononuclear cells (PBMCs) were tested for peptide-specific IFN- release by enzyme-linked immunosorbent spot (ELISpot) assays. Furthermore, expression of the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase in tumor lesions was analyzed by immunohistochemistry before and after vaccination. We also used the ELISpot technique to investigate whether KLH-specific T cells were induced and whether these cells released type 1 (IFN-) and/or type 2 (IL-13) cytokines. Our data show induction of CD8+ T cells specific for the melanosomal peptides MART-1/Melan-A27–35 or tyrosinase1–9, as well as IFN-–releasing KLH-specific T cells, in two of six vaccinated melanoma patients, but do not support an association between the induction of these T cells and clinical responses. |
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Keywords: | Dendritic cells Melanoma T lymphocytes Vaccination |
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