title: Dickkopf-3 Contributes to the Regulation of Anti-Tumor Immune Responses by Mesenchymal Stem Cells.
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.
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Kun-Hui
authors.initials: KH
authors.lastname: Lu
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Amel
authors.initials: A
authors.lastname: Tounsi
authors.affiliation: Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn , Bonn , Germany.
authors.forename: Naveen
authors.initials: N
authors.lastname: Shridhar
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Küblbeck
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Klevenz
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Prokosch
authors.affiliation: Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn , Bonn , Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bald
authors.affiliation: Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn , Bonn , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ) , Heidelberg , Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
keywords: Dickkopf-3; T cell; anti-tumor response; melanoma; mesenchymal stem cell; tumor stroma