CLONAL T-CELL RESPONSES IN TUMOR-INFILTRATING LYMPHOCYTES FROM BOTH REGRESSIVE AND PROGRESSIVE REGIONS OF PRIMARY HUMAN-MALIGNANT MELANOMA

The T cell receptor (TCR) BV variable (V) gene repertoire of tumor inf iltrating lymphocytes (TIL) found in progressive and regressive region s of the same primary human melanomas were characterized by reverse tr anscription coupled polymerase chain reaction (RT-PCR). After surgery, the tumors were divided into different parts which were judged as reg ressive or progressive regions by visual inspection. Subsequently this diagnosis was confirmed by histology. From a total of four primary me lanomas analyzed, 2 were shown to be HLA-A2(+). Only relatively few BV -gene families were expressed at significant levels in each of the sam ples. Comparison of the BV-expression in regressive versus progressive regions of the same tumor revealed major differences in all cases exa mined. Direct sequencing of RT-PCR products indicated that highly expr essed BV-gene families were of clonal origin in both the regressive an d progressive regions. Together, these data strongly suggest the occur rence of clonal T cell responses in both regressive and progressive ar eas of the same primary tumor. The differences in expression of certai n BV-genes may correlate with the functional activity of certain popul ations of tumor-infiltrating T cells.