Dickkopf-3 contributes to the regulation of anti-tumor immune responses by mesenchymal stem cells.

• Main Authors: Kun-Hui eLu, Amel eTounsi, Naveen eShridhar, Günter eKüblbeck, Alexandra eKlevenz, Sandra eProkosch, Tobias eBald, Thomas eTüting, Bernd eArnold
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-12-01
• Series: Frontiers in Immunology
• Subjects: Melanoma; T cell; mesenchymal stem cell; tumor stroma; anti-tumor response; Dickkopf-3
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00645/full
• ISSN: 1664-3224

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.