High frequencies of circulating melanoma-reactive CD8+ T cells in patients with advanced melanoma

• Verfasst von: Letsch, Anne [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: High frequencies of circulating melanoma-reactive CD8+ T cells in patients with advanced melanoma
• Verf.angabe: Anne Letsch, Ulrich Keilholz, Dirk Schadendorf, Dirk Nagorsen, Alexander Schmittel, Eckhard Thiel and Carmen Scheibenbogen
• Umfang: 6 S.
• Fussnoten: Gesehen am 26.02.2019
• Titel Quelle: Enthalten in: International journal of cancer
• Jahr Quelle: 2000
• Band/Heft Quelle: 87(2000), 5, S. 659-664
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/1097-0215(20000901)87:5<659¬AID-IJC7>3.0.CO;2-7
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1588042928

Abstract

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.