Identification of known and novel immunogenic T-cell epitopes from tumor antigens recognized by peripheral blood T cells from patients responding to IL-2-based treatment
In previous studies CD8+ T cells specific for melanocyte antigens have been frequently found in melanoma patients responding to interleukin-2 (IL-2)-based therapies. In our study we analyzed the suitability of using circulating T cells from melanoma patients with clinical response after IL-2-based t...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
14 January 2002
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| In: |
International journal of cancer
Year: 2002, Volume: 98, Issue: 3, Pages: 409-414 |
| ISSN: | 1097-0215 |
| DOI: | https://doi.org/10.1002/ijc.10205 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/ijc.10205 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.10205 
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| Author Notes: | Carmen Scheibenbogen, Yuansheng Sun, Ulrich Keilholz, Mingxia Song, Stefan Stevanovic, Anne Marie Asemissen, Dirk Nagorsen, Eckhard Thiel, Hans-Georg Rammensee and Dirk Schadendorf |
| Summary: | In previous studies CD8+ T cells specific for melanocyte antigens have been frequently found in melanoma patients responding to interleukin-2 (IL-2)-based therapies. In our study we analyzed the suitability of using circulating T cells from melanoma patients with clinical response after IL-2-based therapy to identify novel T-cell epitopes from defined tumor antigens. Using unstimulated peripheral blood mononuclear cells and the interferon-γ (IFN-γ) ELISPOT assay, we studied CD8+ T-cell responses against 5 peptides from the tumor antigen tyrosinase (Tyr) selected by epitope prediction using an HLA-A1-binding computer algorithm. T cells specifically secreting IFN-γ in response to 3 of these 5 peptides, namely, Tyr (454-463), Tyr (146-156) and Tyr (243-251), could be detected in 4 of 4 HLA-A1-positive patients with clinical response. In contrast, no T-cell responses against these peptides were seen in 6 HLA-A1-positive melanoma patients with progressive disease and in 8 healthy subjects. We could generate specific cytotoxic T lymphocytes (CTL) against Tyr (454-463) using peptide-pulsed autologous dendritic cells as antigen-presenting cells. The induced CTLs efficiently killed melanoma cells that express HLA-A1 and tyrosinase. The peptides Tyr (146-156) and Tyr (243-251) had recently been identified as CTL epitopes by other groups. Further ex vivo characterization of the T cells reactive against the novel epitope Tyr (454-463) in 1 patient by multicolor flow cytometry showed specific CD3+/CD8+/IFN-γ+ T cells with frequencies of up to 0.41% of the CD3+/CD8+ T-cell population. Most of this T-cell population also expressed granzyme B. Our data confirm that in patients with tumor regressions induced by immunotherapy or chemoimmunotherapy circulating T cells reactive with tyrosinase epitopes can frequently be detected. Peripheral blood T cells from such patients are a valuable source for screening peptides selected by epitope prediction This strategy facilitates the rapid identification of immunogenic T-cell epitopes that are probable targets of immune-mediated tumor rejection. © 2002 Wiley-Liss, Inc. |
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| Item Description: | Gesehen am 11.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | https://doi.org/10.1002/ijc.10205 |