Restricted T-cell receptor repertoire in melanoma metastases regressing after cytokine therapy

One major rationale for using interleukin-2 and IFN-alpha 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 beta-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.