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Identification of identical TCRs in primary melanoma lesions and tumor free corresponding sentinel lymph nodes

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Abstract

It is generally believed that priming of efficient T-cell responses takes place in peripheral lymphoid tissues. Although this notion has been rigidly proven for infectious diseases, direct evidence for lymph node priming of in vivo T-cell responses against tumors is still lacking. In the present study, we conducted a full and nonbiased comparison of T-cell clonotypes in melanoma lesions and corresponding sentinel lymph nodes. Whereas most tumor lesions comprised a high number of T-cell clonotypes, only a small number of clonally expanded T cells were detected in the draining lymph nodes. Comparative clonotype mapping demonstrated the presence of identical T-cell clonotypes in the tumors and the respective sentinel lymph nodes, only when tumor cells were present in the latter. However, taking advantage of clonotype specific PCR amplification, TCR sequences representing clonally expanded T cells at the tumor site could be detected in the lymph nodes draining the tumors even in the absence of tumor cells. Evidence for the tumor-specific characteristics of these cells was obtained by in situ staining with peptide/HLA class I complexes demonstrating the presence of MART-1/HLA-A2- and MAGE-3/HLA-A2-reactive T cells at the tumor site, as well as in the draining lymph node. Our data indicate that T-cell responses to melanoma are primed in the sentinel lymph node by cross presentation of tumor antigens by dendritic cells.

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Acknowledgements

We wish to thank the Danish Melanoma Group for continued interest and support. Grant support: the work was supported by grants from the Danish Research Council, The Danish Cancer Society, The NOVO NORDISK FOUNDATION, the Deutsche Krebshilfe (grant 10-1845-Be1), and the Bundesminesterium für Bildung und Forschung (IZKF Würzburg, Projekt B17, grant 01 KS 903).

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Authors and Affiliations

  1. Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, 2100, Copenhagen, Denmark

    Per thor Straten, Lars Østergaard Pedersen, Mads Hald Andersen & Tina Seremet

  2. Genomics Laboratory, Institute of Cancer Biology, Danish Cancer Society, 2100, Copenhagen, Denmark

    Christina Dahl & Per Guldberg

  3. Department of Dermatology, School of Medicine, 97080, Würzburg, Germany

    David Schrama, Eva-B. Bröcker & Jürgen C. Becker

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  1. Per thor Straten
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  2. Christina Dahl
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  3. David Schrama
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  4. Lars Østergaard Pedersen
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  5. Mads Hald Andersen
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  7. Eva-B. Bröcker
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  9. Jürgen C. Becker
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Correspondence to Per thor Straten.

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Straten, P.t., Dahl, C., Schrama, D. et al. Identification of identical TCRs in primary melanoma lesions and tumor free corresponding sentinel lymph nodes. Cancer Immunol Immunother 55, 495–502 (2006). https://doi.org/10.1007/s00262-005-0023-8

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  • DOI: https://doi.org/10.1007/s00262-005-0023-8

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