Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells.

Blood eosinophilia in tumor patients treated with interleukin-2 (IL-2) is well known and is regarded as evidence of toxicity or as a side-effect [Lotze et al. (1986) Arch Surg 121:1373-1379; West et al. (1987) N Engl J Med 316:898-905]. We recently described a new local IL-2 approach to therapy for advanced bladder carcinoma that allows, for the first time, high-dose continuous administration of natural interleukin-2 (nIL-2) at the tumor site without side-effects [Huland and Huland (1989) Cancer Res 49:5469-5474]. Tumor-associated eosinophilia of up to 65% (i.e. eosinophils constituting 65% of leukocytes) was seen in four of five patients after treatment, but never before treatment or in untreated controls. Activated eosinophils were attached to bladder tumor cells. Local activation was seen only after natural IL-2 treatment and was determined by cytological criteria and by staining with monoclonal antibody (mAb) EG1 directed against all eosinophil granule proteins and mAb EG2 directed against the active secretory granule proteins of the eosinophils. Bladder cancer cells in urinary sediment also stained with these two mAbs, revealing active degranulation of eosinophils on bladder tumor cells. The number of eosinophils in blood increased, however, without signs of activation. These data constitute strong evidence that activated eosinophils in vivo are involved in the IL-2-induced antitumor response.