Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity.
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.
Johann
Pascal-David
PD
Department of General Paediatrics, University Children's Hospital, Tübingen, Germany.
Vaegler
Martin
M
Gieseke
Friederike
F
Mang
Philippa
P
Armeanu-Ebinger
Sorin
S
Kluba
Torsten
T
Handgretinger
Rupert
R
Müller
Ingo
I
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