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Front Immunol. 2015 Dec 24;6:645. doi: 10.3389/fimmu.2015.00645. eCollection 2015.

Dickkopf-3 Contributes to the Regulation of Anti-Tumor Immune Responses by Mesenchymal Stem Cells.

Author information

1
Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
2
Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn , Bonn , Germany.

Abstract

Mesenchymal stem cells (MSCs) are known to limit immune responses in vivo by multiple soluble factors. Dickkopf-3 (DKK3), a secreted glycoprotein, has recently been identified as a novel immune modulator. Since DKK3 has been reported to be produced by MSCs, we investigated whether DKK3 contributes to the immune suppression of anti-tumor responses by MSCs. Whereas wild-type MSCs inhibited immune responses against two different transplantation tumors, DKK3-deficient MSCs did not affect the rejection process. Increased CD8(+) T cell and reduced M2-type macrophages infiltration was observed in tumors inoculated together with DKK3-deficient MSCs. Thus, DKK3 could alter the composition of the tumor stroma, thereby supporting the MSCs-mediated suppression of immune responses against these tumor transplants.

KEYWORDS:

Dickkopf-3; T cell; anti-tumor response; melanoma; mesenchymal stem cell; tumor stroma

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