Circulating tumor-reactive CD8+ T cells in melanoma patients contain a CD45RA+CCR7- effector subset exerting ex vivo tumor-specific cytolytic activity
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 an...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 15, 2002
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| In: |
Cancer research
Year: 2002, Volume: 62, Issue: 6, Pages: 1743-1750 |
| ISSN: | 1538-7445 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://cancerres.aacrjournals.org/content/62/6/1743
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Im Titel sind die Zeichen + und - hochgestellt Gesehen am 11.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1538-7445 |