title: Anti-TGF-β antibody combined with dendritic cells produce antitumor effects in osteosarcoma.
abstract: BACKGROUND
  We previously reported the combination of tumor cryotreatment with dendritic cells to promote antitumor immunity. The effect of the combination treatment with dendritic cells and antitransforming growth factor-β (anti-TGF-β) antibody on the elimination of regulatory T cells and the inhibition of tumor growth was investigated.
  
  
  OBJECTIVE
  The effects of the combination treatment with dendritic cells and anti-TGF-β antibody on the enhancement of systemic immune responses and inhibition of metastatic tumor growth were investigated in a murine osteosarcoma (LM8) model.
  
  
  METHODS
  To evaluate activation of the immune response, we established the following three groups of C3H mice (60 mice total): (1) excision only; (2) tumor excision and administration of anti-TGF-β antibody; and (3) tumor excision and administration of dendritic cells exposed to cryotreated tumor lysates with anti-TGF-β antibody.
  
  
  RESULTS
  The mice that received dendritic cells exposed to cryotreated tumor lysates with anti-TGF-β antibody showed increased numbers of CD8(+) T lymphocytes, reduced regulatory T lymphocytes in the metastatic lesion, and inhibition of metastatic growth. The combined therapy group showed reduced numbers of regulatory T lymphocytes in the spleen and high serum interferon γ level.
  
  
  CONCLUSIONS
  The control of the inhibitory condition induced by regulatory T cells is important to improve the suppression of the cytotoxic lymphocytes. Combining dendritic cells with anti-TGF-β antibody enhanced the systemic immune response.
  
  
  CONCLUSIONS
  We suggest that our immunotherapy could be developed further to improve the treatment of osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita, Japan. kawano@oita-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawano
authors.forename: Ichiro
authors.initials: I
authors.lastname: Itonaga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsumura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D012516:Osteosarcoma / Q000276:immunology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D016212:Transforming Growth Factor beta