title: Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity.
abstract: BACKGROUND
  Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.
  
  
  METHODS
  In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.
  
  
  RESULTS
  While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.
  
  
  CONCLUSIONS
  Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.
authors.affiliation: Department of General Paediatrics, University Children's Hospital, Tübingen, Germany.
authors.forename: Pascal-David
authors.initials: PD
authors.lastname: Johann
authors.forename: Martin
authors.initials: M
authors.lastname: Vaegler
authors.forename: Friederike
authors.initials: F
authors.lastname: Gieseke
authors.forename: Philippa
authors.initials: P
authors.lastname: Mang
authors.forename: Sorin
authors.initials: S
authors.lastname: Armeanu-Ebinger
authors.forename: Torsten
authors.initials: T
authors.lastname: Kluba
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology*; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology; D012516:Osteosarcoma / Q000276:immunology / Q000473:pathology; D012208:Rhabdomyosarcoma / Q000276:immunology / Q000473:pathology; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured