title: Indoleamine-2,3-dioxygenase in an immunotherapy model for Ewing sarcoma.
abstract: OBJECTIVE
  Interleukin-2 (IL2) transgenic Ewing sarcoma cells reduce tumor growth in vivo and in vitro. In the present study we analyzed the expression of immune suppressive indoleamine-2,3-dioxygenase (IDO) in this model.
  
  
  METHODS
  Expression of IDO was analyzed by polymerase chain reaction. The impact of the cluster of differentiation 137 (CD137)/CD137 ligand (CD137L) co-stimulatory system on expression of IDO and different cytokines was analyzed both in vivo and in vitro.
  
  
  RESULTS
  Tumors that developed in vivo in the presence of IL2 transgenic tumor cells expressed IDO. The presence of CD137L transgenic tumor cells led to down-regulation of IDO. Further in-vitro analysis of this phenomenon indicated that IDO was expressed in tumor cells as a consequence of interferon-gamma produced by lymphocytes in response to IL2. Depending on the concentration of IL2, stimulation of CD137 increased or reduced cytokine production in lymphocytes.
  
  
  CONCLUSIONS
  Our data indicate that the CD137/CD137L pathway can modulate the immune response against Ewing sarcoma cells.
authors.affiliation: University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Max
authors.affiliation: University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Caspar D
authors.initials: CD
authors.lastname: Kühnöl
authors.affiliation: University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany Laboratory of Transplantation Biology, Children's Cancer Research Center, Technical University of Munich, Munich, Germany Department of Pediatrics, Technical University of Munich, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Liguo
authors.initials: L
authors.lastname: Niu
authors.affiliation: University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany martin.staege@medizin.uni-halle.de juergen.foell@klinik.uni-regensburg.de.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Staege
authors.affiliation: University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital Regensburg, Regensburg, Germany martin.staege@medizin.uni-halle.de juergen.foell@klinik.uni-regensburg.de.
authors.forename: Jürgen L
authors.initials: JL
authors.lastname: Föll
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000502:physiology*; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007376:Interleukin-2; D053278:OX40 Ligand; D012333:RNA, Messenger; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D007371:Interferon-gamma
keywords: CD137; Ewing sarcoma; Interleukin-2; immune escape; indoleamine-2,3-dioxygenase