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Restricted T-Cell Receptor Repertoire in Melanoma Metastases Regressing after Cytokine Therapy¹

Medizinische Klinik und Poliklinik V, Hospitalstrasse 3 [M. W., T. M.] and Research Program Applied Tumor Virology, Deutsches Krebsforschungszentrum [M. P.], 69115 Heidelberg, and Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin-Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin [C. S., E. T., U. K.], Germany

One major rationale for using interleukin-2 and IFN- in cancer immunotherapy is to activate tumor-specific T cells at the tumor site. To study the in situ T-cell response, we determined the T-cell receptor (TCR) repertoire in six melanoma metastases regressing after cytokine treatment obtained from five patients. Sequence analysis of overexpressed TCR ß-chain variable regions revealed the presence of clonally expanded T cells and also of T cells with highly homologous complementarity determining regions 3 in all five patients. This finding indicates that the T-cell response in regressing melanoma lesions is dominated by T cells directed toward a limited number of epitopes and that epitope-specific T cells frequently use a highly restricted TCR repertoire.

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				J. Zhou, M. E. Dudley, S. A. Rosenberg, and P. F. Robbins Selective Growth, In Vitro and In Vivo, of Individual T Cell Clones from Tumor-Infiltrating Lymphocytes Obtained from Patients with Melanoma J. Immunol., December 15, 2004; 173(12): 7622 - 7629. [Abstract] [Full Text] [PDF]