Regulatory T cells stimulate B7-H1 expression in myeloid-derived suppressor cells in ret melanomas

• Verfasst von: Fujimura, Taku [VerfasserIn]
• Verfasst von: Ring, Sabine [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Verfasst von: Mahnke, Karsten [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Titel: Regulatory T cells stimulate B7-H1 expression in myeloid-derived suppressor cells in ret melanomas
• Verf.angabe: Taku Fujimura, Sabine Ring, Viktor Umansky, Karsten Mahnke and Alexander H. Enk
• Jahr: 2012
• Jahr des Originals: 2011
• Umfang: 8 S.
• Fussnoten: Published online 22 December 2011 ; Gesehen am 04.06.2018
• Titel Quelle: Enthalten in: The journal of investigative dermatology
• Ort Quelle: Amsterdam : Elsevier, 1938
• Jahr Quelle: 2012
• Band/Heft Quelle: 132(2012), 4, Seite 1239-1246
• ISSN Quelle: 1523-1747
• DOI: doi:10.1038/jid.2011.416
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1575954575

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells, and they promote an immunosuppressive environment in tumor-bearing hosts. To characterize MDSCs in melanoma, we examined the expression of inhibitory B7 molecules by CD11b+Gr1+ cells isolated from mice with transplantable ret tumors. B7 molecules were expressed on CD11b+Gr1+ cells, which also expressed CD124 and inducible nitric oxide synthase, thus verifying their relation to MDSCs. In developing melanomas, CD11b+Gr1+ cells express only low levels of B7-H1. In contrast, B7-H1 is upregulated in large tumors, and functional analysis demonstrates that CD11b+Gr-1+ cells suppress the proliferation of CD4+ T cells through B7-H1. Depletion of regulatory T cells (Tregs) significantly downregulated the expression of B7-H1, B7-H3, and B7-H4 on MDSCs and reduced tumor growth, indicating a concerted immunosuppressive activity of Tregs and MDSCs. No differences in the suppressive function of MDSCs between CD25-depleted and non-depleted mice were recorded. Instead, tumor-derived MDSCs from Treg-depleted hosts produced less IL-10 and more IFN-γ as compared with Treg-harboring mice. These studies indicate that Tregs in tumors not only suppress effector T cells directly, but also modify the phenotype of tumor-infiltrating CD11b+ cells to express inhibitory B7-H molecules and to produce IL-10.