Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity
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Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity. / Johann, Pascal-David; Vaegler, Martin; Gieseke, Friederike; Mang, Philippa; Armeanu-Ebinger, Sorin; Kluba, Torsten; Handgretinger, Rupert; Müller, Ingo.
In: BMC CANCER, Vol. 10, 01.01.2010, p. 501.Research output: SCORING: Contribution to journal › SCORING: Journal article › Transfer › peer-review
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TY - JOUR
T1 - Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity
AU - Johann, Pascal-David
AU - Vaegler, Martin
AU - Gieseke, Friederike
AU - Mang, Philippa
AU - Armeanu-Ebinger, Sorin
AU - Kluba, Torsten
AU - Handgretinger, Rupert
AU - Müller, Ingo
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Bone Marrow Cells
KW - Bone Neoplasms
KW - Cell Differentiation
KW - Cell Proliferation
KW - Child
KW - Child, Preschool
KW - Coculture Techniques
KW - Humans
KW - Immunophenotyping
KW - Infant
KW - Infant, Newborn
KW - Killer Cells, Natural
KW - Mesenchymal Stromal Cells
KW - Neuroblastoma
KW - Osteosarcoma
KW - Rhabdomyosarcoma
KW - Sarcoma, Ewing
KW - Stromal Cells
KW - Tumor Cells, Cultured
U2 - 10.1186/1471-2407-10-501
DO - 10.1186/1471-2407-10-501
M3 - SCORING: Journal article
C2 - 20858262
VL - 10
SP - 501
JO - BMC CANCER
JF - BMC CANCER
SN - 1471-2407
ER -