INDUCTION OF 2 DISTINCT NATURAL-KILLER-CELL POPULATIONS, ACTIVATED T-CELLS AND ANTINEOPLASTIC CYTOKINES, BY INTERLEUKIN-2 THERAPY IN CHILDREN WITH SOLID TUMORS

Children with poor prognoses regarding solid tumors have benefited fro m autologous bone marrow transplantation as a treatment modality. Post transplantation adjuvant interleukin-2 (IL-2) therapy has previously b een shown to improve prognosis in adults with neoplastic disease. The improved survival probability has been attributed to IL-2-mediated sti mulation of the immune system and its antineoplastic activity. In this study, 10 pediatric patients with solid tumors in complete remission after autologous stem cell transplantation were treated with recombina nt IL-2, which was administered in three 5-day cycles of continuous in travenous infusions with a 2-week rest in between cycles. We demonstra ted that IL-2 therapy enhanced transplantation-related stimulation of the immune system, on both the cellular and humoral levels. Peripheral blood T and natural killer (NK) cells increased by the factors four a nd 14, respectively. Activation of the immune system was demonstrated by significantly elevated levels of soluble IL-2 receptor (IL-2R) and increased CD25 surface expression on T lymphocytes. IL-2 also induced significant proliferation of the CD56(bright) NK-cell subpopulation th at appears post-bone marrow transplant (BMT) and is found only in mini mal amounts in normal controls. In vivo and in vitro production of tum or cytotoxic cytokines tumor necrosis factor-alpha (TNF-alpha) and int erferon-gamma (IFN-gamma) was significantly stimulated following IL-2 therapy, further indicating IL-2-mediated stimulation of the antineopl astic activity of the immune system.