title: An experimental study of dendritic cells-mediated immunotherapy against intracranial gliomas in rats.
abstract: OBJECTIVE
  To investigate the effect of dendritic cells(DC) pulsed with apoptotic tumor cells for treatment of intracranial gliomas in rats.
  
  
  METHODS
  C6 glioma cells were injected into brain of Wistar rats under stereotactic monitor to establish an animal model of glioma. The precursors of DCs were isolated from bone marrow of rats, stimulated in vitro with recombinent rat granulocyte-macrophage colony-stimulating factor (rrGM-CSF) and interleukin-4 (rrIL-4). These DCs were then pulsed ex vivo with apoptotic C6 glioma cells induced by heating and subsequently injected subcutaneously into rats harboring intracranial C6 glioma. Rats were treated with five weekly subcutaneous injections of either control media, unpulsed DCs, or DCs pulsed with apoptotic tumor cells. The animals were followed for survival, volume of tumor by MRI, CD8 + T cells, cytotoxicity assay in vitro and proliferational function of lymphocytes in peripheral blood were determined by flow cytometry(FCM). The concentration of cytokines interferon-gamma (IFN-gamma) and interleukin-10(IL-10) were monitored through enzyme-linked immunosorbent assay(ELISA) using ELISAkit.
  
  
  RESULTS
  Our results indicated that C6 glioma model rats treated with apoptotic tumor cells pulsed DCs prolonged survival, inhibited the tumor growth and increased the level of CD8 + T lymphocytes in peripheral blood comparing with control group. Cytotoxicity assay suggested that vaccination with these apoptotic cells pulsed DCs can induce cytotoxic T lymphocytes response against C6 tumor cells compared with control group. Furthermore, significantly enhanced IFN-gamma and reduced IL-10(even undetectable) were observed in peripheral blood of rats treated with pulsed-DCs. No evident autoimmune response were detected.
  
  
  CONCLUSIONS
  Our data demonstrated that systemic vaccination with DCs pulsed with apoptotic cells is a safe and effective immunotherapy for intracranial glioma.
authors.affiliation: Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China. zhu_xinmei@yahoo.com.cn
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhu
authors.forename: Chuanzhen
authors.initials: C
authors.lastname: Lu
authors.forename: Baoguo
authors.initials: B
authors.lastname: Xiao
authors.forename: Jian
authors.initials: J
authors.lastname: Qiao
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016753:Interleukin-10; D007371:Interferon-gamma