Neuroblastoma cells expressing mature IL-18, but not proIL-18, induce a strong and immediate antitumor immune response.
Retroviral constructs were designed to express the novel cytokine interleukin 18 (IL-18), also known as interferon-gamma-inducing factor, in a murine neuroblastoma cell line [neuro-2a (N-2a)] to examine the effects of IL-18 expression on tumorigenicity. N-2a cells expressing proIL-18 (N-2a/IL-18p) were as tumorigenic as parental N-2a cells, whereas N-2a cells engineered to secrete mature IL-18 (N-2a/IL-18m) were nontumorigenic. Inoculation of mice with N-2a/IL-18m generated immediate immunity to parental N-2a. N-2a/IL-18m formed tumors in mice depleted of CD4+ and CD8+ T cells, suggesting that the antitumor immune response was T cell mediated. The resulting T-helper (Th) immune response was also characterized in vitro and had a large Th1 component based on in vitro production of the cytokines IFN-gamma and granulocyte macrophage colony-stimulating factor in response to tumor cells and IL-18.
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA.
J G
JG
Heuer
C
C
Tucker-McClung
R A
RA
Hock
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000096:biosynthesis; D016867:Immunocompromised Host / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000276:immunology*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis / Q000276:immunology*; D011863:Radioimmunoassay; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000235:genetics; D053724:Receptors, Interleukin-18; D012016:Reference Values; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; C508573:Il18r1 protein, mouse; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D011498:Protein Precursors; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; C043830:interleukin 1 precursor