RESTRICTION OF T-CELL RECEPTOR V-BETA REPERTOIRE IN MELANOMA METASTASIS RESPONDING TO IMMUNOTHERAPY

Restriction of the T cell receptor repertoire suggesting ongoing speci fic immune mechanisms has recently been described in melanoma tissue b y several groups of investigators, The functional relevance for immuno therapy of melanoma, however, has not been established, We studied the T cell receptor repertoire in two melanoma metastases of a patient wi th a mixed response to immunotherapy. Expression of T cell receptor V beta regions was determined by subgroup-specific semiquantitative RNA polymerase chain reaction (PCR), In the regressing skin lesion a restr icted expression of the T cell receptor repertoire and overexpression of three V beta subgroup genes was found; no restriction was present i n the simultaneously progressing skin lesion of the same patient, comp ared with peripheral blood lymphocytes, Comparison of T cell receptor V beta gene expression in two metastatic lesions of a patient with sim ultaneously growing skin metastases, who did not receive immunotherapy , revealed only minor differences, These observations show for the fir st time an association between restricted T cell receptor repertoire a nd responsiveness of melanoma to immunotherapy and suggest a role of T cells using the overexpressed V beta genes for the cytokine-induced t umour regression.