High frequencies of circulating melanoma-reactive CD8+ T cells in patients with advanced melanoma
To determine whether circulating tumor-reactive T cells are present in melanoma patients, unstimulated T cells from peripheral blood were tested for recognition of HLA-A2- or HLA-A1-matched melanoma cell lines using the ELISPOT assay. Eleven out of 19 patients with metastatic melanoma had a T-cell r...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 July 2000
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| In: |
International journal of cancer
Year: 2000, Volume: 87, Issue: 5, Pages: 659-664 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/1097-0215(20000901)87:5<659::AID-IJC7>3.0.CO;2-7 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/1097-0215(20000901)87:5<659::AID-IJC7>3.0.CO;2-7 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0215%2820000901%2987%3A5%3C659%3A%3AAID-IJC7%3E3.0.CO%3B2-7 
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| Author Notes: | Anne Letsch, Ulrich Keilholz, Dirk Schadendorf, Dirk Nagorsen, Alexander Schmittel, Eckhard Thiel and Carmen Scheibenbogen |
| Summary: | To determine whether circulating tumor-reactive T cells are present in melanoma patients, unstimulated T cells from peripheral blood were tested for recognition of HLA-A2- or HLA-A1-matched melanoma cell lines using the ELISPOT assay. Eleven out of 19 patients with metastatic melanoma had a T-cell response with up to 0.81%, 0.78%, 0.53%, 0.12%, 0.10%, 0.09%, 0.07%, 0.06%, 0.06%, 0.04%, and 0.04% of peripheral blood mononuclear cells (PBMC) secreting IFNγ upon exposure to various HLA-A2- or HLA-A1-matched melanoma cell lines. These T-cell responses were mediated by CD8+ T cells and could specifically be blocked by an anti-HLA-A2 antibody in HLA-A2-positive patients. Separation experiments performed in one melanoma patient showed tumor-reactive T cells in both the CD8+ effector T cell (CD45RA+/IFNγ+) as well as the CD8+ memory T-cell compartment (CD45RO+/IFNγ+). In 3 out of 5 patients, in whom autologous cell lines were available, similar frequencies of T cells in response to HLA-A1- or HLA-A2-matched allogeneic and autologous tumor cells were observed, while 2 patients had a T-cell response restricted to either the autologous or the allogeneic cell lines. These results give evidence for the presence of tumor-reactive CD8+ T cells in more than half of melanoma patients tested. Although some of these patients have clinical evidence for an immunological-mediated tumor control, several patients have growing tumors suggesting presence of escape mechanisms. |
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| Item Description: | Gesehen am 26.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/1097-0215(20000901)87:5<659::AID-IJC7>3.0.CO;2-7 |