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BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

Authors: Pascal-David Johann, Martin Vaegler, Friederike Gieseke, Philippa Mang, Sorin Armeanu-Ebinger, Torsten Kluba, Rupert Handgretinger, Ingo Müller

Published in: BMC Cancer | Issue 1/2010

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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.
Appendix
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Metadata
Title
Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity
Authors
Pascal-David Johann
Martin Vaegler
Friederike Gieseke
Philippa Mang
Sorin Armeanu-Ebinger
Torsten Kluba
Rupert Handgretinger
Ingo Müller
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-501

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