Subcutaneous administration of interleukin-2 triggers Fcgamma receptor I expression on human peripheral blood neutrophils in solid and hematologic malignancies.
Freshly isolated human polymorphonuclear cells (PMNCs) constitutively express Fcgamma receptor (Fc-gammaR) II and FcgammaRIII on the cell surface but not FcgammaRI. Cytokines such as interferon-gamma (IFNgamma), granulocyte-macrophage colony-stimulating factor (CSF), and granulocyte-CSF trigger FcgammaRI expression on (PMNCs). Because PMNCs express interleukin (IL)-2 receptor, we investigated whether IL-2 can induce FcgammaRI expression on PMNCs isolated from IL-2-treated metastatic renal cell carcinoma (MRCC) and low-grade non-Hodgkin lymphoma (LGNHL) patients. Pretherapy flow cytometry analysis of Fcgamma receptors on PMNCs did not show FcgammaRI expression. Interestingly, 3 days after therapy, PMNCs displayed a detectable amount of FcgammaRI on the cell surface. Kinetic studies on the in vivo effects of IL-2 on MRCC patients showed that FcgammaRI was transiently expressed, starting within 3-6 days of therapy, remaining expressed for 10-15 days, and rapidly declining, whereas such expression remained stable for months in LGNHL patients. In contrast, Fc-gammaRII was not affected. In addition, FcgammaRI+ PMNCs coated in vitro with a bispecific antibody Fab anti-FcgammaRI x anti-HER-2/neu formed intercellular conjugates with a human HER-2/neu-transfected 3T3 cell line (HER-2/neu-3T3). Interleukin-2 treatment increased the number of FcgammaRIII low eosinophils, leading to a change in FcgammaRIII distribution among granulocyte cell subsets. In vitro IL-2 treatment of purified PMNCs failed to generate Fc-gammaRI expression, suggesting that IL-2 indirectly causes FcgammaRI expression. During the IL-2 administration, we did not observe significant changes in IFNgamma serum level. In conclusion, our observation may be used to potentiate the antitumor effects of IL-2 in novel immunotherapy regimens, perhaps by redirecting FcgammaRI+ PMNCs against cancer cells by heteroconjugate antibodies and monitoring the biologic activity of subcutaneous IL-2 in cancer patients.
Sconocchia
G
G
Institute of Tissue Typing and Dialysis, Consiglio Nazionale delle Ricerche, Rome, Italy.
Cococcetta
N Y
NY
Campagnano
L
L
Amadori
S
S
Iorio
B
B
Boffo
V
V
Ferdinandi
V
V
Del Principe
I
I
Adorno
D
D
Casciani
C U
CU
D000293:Adolescent; D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000556:secondary; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*
D018033:Antibodies, Bispecific; D016207:Cytokines; D007376:Interleukin-2; D017452:Receptors, IgG; D007371:Interferon-gamma