Subcutaneous administration of interleukin-2 triggers Fc gamma receptor I expression on human peripheral blood neutrophils in solid and hematologic malignancies

Freshly isolated human polymorphonuclear cells (PMNCs) constitutively expre ss Fc gamma receptor (Fc gammaR) II and Fc gamma RIII on the cell surface b ut not Fc gamma RI. Cytokines such as interferon-gamma (IFN-gamma), granulo cyte-macrophage colony-stimulating factor (CSF), and granulocyte-CSF trigge r Fc gamma RI expression on (PMNCs). Because PMNCs express interleukin (IL) -2 receptor, we investigated whether IL-2 can induce Fc gamma RI expression on PMNCs isolated from IL-2-treated metastatic renal cell carcinoma (MRCC) and low-grade non-Hodgkin lymphoma (LGNHL) patients. Pretherapy flow cytom etry analysis of Fc receptors on PMNCs did not show Fc gamma RI expression. Interestingly, 3 days after therapy, PMNCs displayed a detectable amount o f Fc gamma RI on the cell surface. Kinetic studies on the in vivo effects o f IL-2 on MRCC patients showed that Fc gamma RI was transiently expressed, starting within 3-6 days of therapy, remaining expressed for 10-15 days, an d rapidly declining, whereas such expression remained stable for months in LGNHL patients. In contrast, Fc gamma RII was not affected. In addition, Fc gamma RI+ PMNCs coated in vitro with a bispecific antibody Fab anti-Fc gam ma RI x anti-HER-2/neu formed intercellular conjugates with a human HER-2/n eu-transrected 3T3 cell line (HER-2/neu-3T3). Interleukin-2 treatment incre ased the number of Fc gamma RIII low eosinophils, leading to a change in Fc -yRIII distribution among granulocyte cell subsets. In vitro IL-2 treatment of purified PMNCs failed to generate Fc gamma RI expression, suggesting th at IL-2 indirectly causes Fc gamma RI expression. During the IL-2 administr ation, we did not observe significant changes in IFN gamma serum level. In conclusion, our observation may be used to potentiate the antitumor effects of IL-2 in novel immunotherapy regimens, perhaps by redirecting Fc gamma R I+ PMNCs against cancer cells by heteroconjugate antibodies and monitoring the biologic activity of subcutaneous IL-2 in cancer patients.