Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25-FoxP3- T cells

Sara M. Centuori, Malika Trad, Collin J. Lacasse, Darya Alizadeh, Claire B. Larmonier, Neale T. Hanke, Jessica Kartchner, Nona Janikashvili, Bernard Bonnotte, Nicolas Larmonier, Emmanuel Katsanis

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

MDSCs and Tregs play an essential role in the immunosuppressive networks that contribute to tumor-immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-talk between MDSC and Treg remain incompletely defined. Previous reports have suggested that MDSC may contribute to Treg induction in cancer. Herein, we provide evidence that tumor-induced gr-MDSCs, endowed with the potential of suppressing conventional T Lc, surprisingly impair TGF-β1-mediated generation of CD4+CD25+FoxP3+ iTregs. Furthermore, gr-MDSCs impede the proliferation of nTregs without, however, affecting FoxP3 expression. Suppression of iTreg differentiation from naïve CD4+ cells by gr-MDSC occurs early in the polarization process, requires inhibition of early T cell activation, and depends on ROS and IDO but does not require arginase 1, iNOS, NO, cystine/cysteine depletion, PD-1 and PD-L1 signaling, or COX-2. These findings thus indicate that gr-MDSCs from TB hosts have the unanticipated ability to restrict immunosuppressive Tregs.

Original languageEnglish (US)
Pages (from-to)987-997
Number of pages11
JournalJournal of Leukocyte Biology
Volume92
Issue number5
DOIs
StatePublished - Nov 1 2012

Keywords

  • Cancer
  • Immunosuppression
  • MDSC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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