title: Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma.
abstract: We attempted to enhance the antitumor effects of tumor lysate-pulsed dendritic cells by eliminating regulatory T cells. The combinatorial effects of dendritic cells and agonist anti-glucocorticoid-induced tumor necrosis factor receptor (anti-GITR) antibodies were investigated with respect to enhancement of the systemic immune response, elimination of regulatory T cells, and inhibition of tumor growth. To determine whether the combination of dendritic cells and anti‑GITR antibodies could enhance systemic immune responses and inhibit primary tumor growth in a murine osteosarcoma (LM8) model. We established the following 4 groups of C3H mice (20 mice in total): i), control IgG-treated mice; ii), tumor lysate-pulsed dendritic cell‑treated mice; iii), agonist anti-GITR antibody-treated mice; and iv), agonist anti-GITR antibody- and tumor lysate-pulsed dendritic cell‑treated mice.The mice that received the agonist anti-GITR antibodies and tumor lysate-pulsed dendritic cells displayed inhibited primary growth, prolonged life time, reduced numbers of regulatory T lymphocytes in the spleen, elevated serum interferon-γ levels, increased number of CD8+ T lymphocytes. The mice that received combined therapy had reduced level of immunosuppressive cytokines in tumor tissue and serum. Combining agonist anti-GITR antibodies with tumor lysate-pulsed dendritic cells enhanced the systemic immune response. These findings provide further support for the continued development of agonist anti-GITR antibodies as an immunotherapeutic strategy for osteosarcoma. We suggest that our proposed immunotherapy could be developed further to improve osteosarcoma treatment.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Itonaga
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsumura
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000276:immunology*; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007167:Immunotherapy; D051379:Mice; D012516:Osteosarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D053450:Glucocorticoid-Induced TNFR-Related Protein; C106544:Tnfrsf18 protein, mouse