T-CELL RECEPTOR-BETA VARIABLE REGION DIVERSITY IN MELANOMA METASTASESAFTER INTERLEUKIN 2-BASED IMMUNOTHERAPY

Limited T-cell receptor (TCR) repertoire of tumorinfiltrating lymphocy tes has been found in melanoma metastases and spontaneously regressing melanoma, Immunotherapy with INF-alpha/interleukin 2 can induce tumor regression in a proportion of patients with metastatic melanoma, We a nalyzed the gene expression of the TCR-beta variable (V beta) region o f tumor-infiltrating lymphocytes from 16 melanoma metastases by subgro up-specific semiquantitative RNA PCR to investigate the influence of i mmunotherapy on the TCR pattern, In five progressing metastases before or after immunotherapy, no overexpression of V beta gene families was detectable, whereas in seven of seven metastases responding to IFN-al pha/interleukin 2 one to four V beta gene families were overexpressed, Preferential usage of certain V beta gene subgroups in patients shari ng the same HLA class I molecules suggests a T-cell response to domina nt public epitopes. Analysis of multiple specimens from the same patie nts gives evidence that this strong oligoclonal T-cell selection is in duced or at least augmented by immunotherapy, supporting the functiona l relevance of this finding.