In vivo cytokine responses to interleukin-2 immunotherapy after autologousstem cell transplantation in children with solid tumors

The potent immunostimulatory cytokine interleukin-2 (IL-2) has been extensi vely investigated for its potential to induce anti-tumor immunity in a numb er of tumor models. Only recently the complex interplay of mutually suppres sive or supportive cytokines of the IL-2-induced network of cytokines has b een better characterized. The aim of this study was to assess which of thes e in vitro findings are reproducible in vivo in recipients of stem cell tra nsplants (SCT), since in these patients longlasting impairments in cytokine inducibility have been described, We have therefore studied the kinetics o f putative modulators and mediators of IL-2-induced immune activation, name ly IL-1 beta, IL-4, IL-5, IL-IO, IL-12, soluble Fas ligand (sFasL), and GM- CSF during IL-2 therapy. All patients were children or adolescents sufferin g from solid tumors with poor prognosis who received three 5-day courses of high-dose intravenous IL-2 as an adjuvant to their radio-chemotherapy and autologous SCT, While IL-1 beta, IL-4 and IL-12 were not, and sFasL, was on ly mildly affected by the IL-2 therapy, we observed a consistent and early rise of IL-10, IL-5, and GR I-CSF. These increases were rapidly reversible after discontinuation of IL-2 therapy. The inducibility of IL-10, IL-5 and GM-CSF was more pronounced with increasing time from the SCT, and in the th ird cycle reached an order of magnitude as in high-dose IL-2 patients witho ut SCT, Together with the abundant in vitro data, these findings mag help d evise a combination immunotherapy permitting stronger anti-tumor effects, b ut lesser adverse effects.