title: Cytokines in neuroblastoma: from pathogenesis to treatment.
abstract: Cytokines released by cancer cells or by cells of the tumor microenvironment stimulate angiogenesis, act as autocrine or paracrine growth factors for malignant cells, promote tumor cell migration and metastasis or create an immunosuppressive microenvironment. These tumor-promoting effects of cytokines also apply to neuroblastoma (NB), a pediatric neuroectodermal malignancy with frequent metastatic presentation at diagnosis and poor prognosis. IL-6 and VEGF are the best characterized cytokines that stimulated tumor growth and metastasis, while others such as IFN-γ can exert anti-NB activity by inducing tumor cell apoptosis and inhibiting angiogenesis. On the other hand, cytokines are part of the anti-NB therapeutic armamentarium, as exemplified by IL-2 and granulocyte-macrophage colony stimulating factor that potentiate the activity of anti-NB antibodies. These recent results raise hope for more efficacious treatment of this ominous pediatric malignancy.
authors.affiliation: Laboratory of Oncology, G Gaslini Institute, Largo G Gaslini 5, 16148 Genova, Italy. vitopistoia@ospedale-gaslini.ge.it
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Borgonovo
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D000068258:Bevacizumab; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009447:Neuroblastoma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000276:immunology*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016207:Cytokines; D005732:Gangliosides; D007371:Interferon-gamma; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; D042442:Vascular Endothelial Growth Factors; D000093242:Interleukin-6 Inhibitors; C019403:ganglioside, GD2