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 journalSCORING: Journal articleTransferpeer-review

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Johann, P-D, Vaegler, M, Gieseke, F, Mang, P, Armeanu-Ebinger, S, Kluba, T, Handgretinger, R & Müller, I 2010, 'Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity', BMC CANCER, vol. 10, pp. 501. https://doi.org/10.1186/1471-2407-10-501

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@article{e1ec57239d324a189c8dacda37db639e,
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.",
keywords = "Adolescent, Bone Marrow Cells, Bone Neoplasms, Cell Differentiation, Cell Proliferation, Child, Child, Preschool, Coculture Techniques, Humans, Immunophenotyping, Infant, Infant, Newborn, Killer Cells, Natural, Mesenchymal Stromal Cells, Neuroblastoma, Osteosarcoma, Rhabdomyosarcoma, Sarcoma, Ewing, Stromal Cells, Tumor Cells, Cultured",
author = "Pascal-David Johann and Martin Vaegler and Friederike Gieseke and Philippa Mang and Sorin Armeanu-Ebinger and Torsten Kluba and Rupert Handgretinger and Ingo M{\"u}ller",
year = "2010",
month = jan,
day = "1",
doi = "10.1186/1471-2407-10-501",
language = "English",
volume = "10",
pages = "501",
journal = "BMC CANCER",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",

}

RIS

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 -