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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Hauptverfasser: Letsch, Anne (VerfasserIn) , Schadendorf, Dirk (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 July 2000
In: International journal of cancer
Year: 2000, Jahrgang: 87, Heft: 5, Pages: 659-664
ISSN:1097-0215
DOI:10.1002/1097-0215(20000901)87:5<659::AID-IJC7>3.0.CO;2-7
Online-Zugang: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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Verfasserangaben:Anne Letsch, Ulrich Keilholz, Dirk Schadendorf, Dirk Nagorsen, Alexander Schmittel, Eckhard Thiel and Carmen Scheibenbogen

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520 |a 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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