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.
Willhauck
Martina
M
Medizinische Klinik und Poliklinik V, Hospitalstrasse 3, 69115 Heidelberg, Germany.
Scheibenbogen
Carmen
C
Pawlita
Michael
M
Möhler
Thomas
T
Thiel
Eckhard
E
Keilholz
Ulrich
U
D000595:Amino Acid Sequence; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D016898:Interferon-alpha; D007376:Interleukin-2; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell