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

Taku Fujimura, Sabine Ring, Viktor Umansky, Karsten Mahnke, Alexander H. Enk

Research output: Contribution to journalArticle

84 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1239-1246
Number of pages8
JournalJournal of Investigative Dermatology
Volume132
Issue number4
DOIs
Publication statusPublished - 2012 Apr

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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