Circulating tumor-reactive CD8+ T cells in melanoma patients contain a CD45RA+CCR7- effector subset exerting ex vivo tumor-specific cytolytic activity

• Verfasst von: Valmori, Danila [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: Circulating tumor-reactive CD8+ T cells in melanoma patients contain a CD45RA+CCR7- effector subset exerting ex vivo tumor-specific cytolytic activity
• Verf.angabe: Danila Valmori, Carmen Scheibenbogen, Valerie Dutoit, Dirk Nagorsen, Anne Marie Asemissen, Verena Rubio-Godoy, Donata Rimoldi, Philippe Guillaume, Pedro Romero, Dirk Schadendorf, Martin Lipp, Pierre-Yves Dietrich, Eckhard Thiel, Jean-Charles Cerottini, Danielle Liénard, and Ulrich Keilholz
• E-Jahr: 2002
• Jahr: March 15, 2002
• Umfang: 8 S.
• Fussnoten: Im Titel sind die Zeichen + und - hochgestellt ; Gesehen am 11.11.2020
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 2002
• Band/Heft Quelle: 62(2002), 6, Seite 1743-1750
• ISSN Quelle: 1538-7445
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1738415678

Abstract

To defend the host from malignancies, the immune system can spontaneouslyraise CD8+ T-cell responses against tumor antigens. Investigatingthe functional state of tumor-reactive cytolytic T cells in cancer patients is a key step for understanding the role of these cells in tumor immunosurveillance and for evaluating the potential of immunotherapeutic approaches of vaccination against cancer. In this study we identified a subset of circulating tumor-reactive CD8+ T lymphocytes, which specifically secreted IFN-γ after exposition to autologous tumor cell lines in stage IV metastatic melanoma patients. Additional phenotypic characterization using multicolor flow cytometry revealed that a significant fraction of these cells were CD45RA+CCR7−, a phenotype that has been proposed recently to characterize cytolytic effectors potentially able to home into inflamed tissues. In the case of an HLA-A2-expressing patient, the antigen specificity of this population was identified by using HLA-A2/peptide multimers incorporating a tyrosinase-derived peptide. Consistently with their phenotypic characteristics, A2/tyrosinase peptide multimer+ CD8+ T cells, isolated by cell sorting, were directly lytic ex vivo and able to specifically recognize tyrosinase-expressing tumor cells. Overall, these results provide the first evidence that a proportion of melanoma patients have circulating tumor-reactive T cells, which are lytic effectors cells.