ACTIVATION MARKERS ON T-CELLS INFILTRATING MELANOMA METASTASES AFTER THERAPY WITH DINITROPHENYL-CONJUGATED VACCINE

Treatment of metastatic melanoma patients with an autologous vaccine m odified by the hapten, dinitrophenyl (DNP), produces a striking immuno logical effect:the induction of clinically evident inflammatory respon ses in metastatic tumors. Histological examination shows these tumors to be infiltrated with T lymphocytes. We studied the expression of act ivation markers on those cells and compared them with matched peripher al blood lymphocytes (PBL) and with lymphocytes extracted from metasta ses before treatment with DNP-conjugated vaccine. The median fraction of cells that were T cells in post-vaccine tumors was 41%, as compared with 9% in pre-treatment tumors, and those T cells were predominantly CD8+ (mean CD8/CD4 ratio = 5.0). A high proportion of both pre- and po st-treatment infiltrating t cells expressed HLA-DR (mean +/- SE = 48% +/- 4%), CD69 (56% +/- 7%), and ganglioside GD3 (68% +/- 5%). This dis tinguished them from matched PBL in which expression of those markers was significantly lower (HLA-DR+ 10% +/- 2%; CD69 + 2% +/- 0.4%; GD3 = 49% +/- 4%). These changes were not accompanied by increase cell-surf ace expression of interleukin-2 (IL-2) receptors, either CD25 or p75, which were expressed by 1%-2% and 12% of tumor-infiltrating lymphocyte s (TIL), respectively. The pattern of activation marker expression tha t we identified appears to be characteristic of tissue T cells with th e memory phenotype. The low expression of IL-2 receptors could indicat e functional impairment of TIL in situ, perhaps because of inhibitory molecules produced by melanoma cells.