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

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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 2012

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T-Lymphocytes
Neoplasms
Immunosuppressive Agents
Tumor Escape
Arginase
Cystine
Myeloid-Derived Suppressor Cells
Cysteine

Keywords

  • Cancer
  • Immunosuppression
  • MDSC

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25-FoxP3- T cells. / Centuori, Sara M.; Trad, Malika; Lacasse, Collin J.; Alizadeh, Darya; Larmonier, Claire B; Hanke, Neale T.; Kartchner, Jessica; Janikashvili, Nona; Bonnotte, Bernard; Larmonier, Nicolas; Katsanis, Emmanuel.

In: Journal of Leukocyte Biology, Vol. 92, No. 5, 11.2012, p. 987-997.

Research output: Contribution to journalArticle

Centuori, Sara M. ; Trad, Malika ; Lacasse, Collin J. ; Alizadeh, Darya ; Larmonier, Claire B ; Hanke, Neale T. ; Kartchner, Jessica ; Janikashvili, Nona ; Bonnotte, Bernard ; Larmonier, Nicolas ; Katsanis, Emmanuel. / Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-β-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25-FoxP3- T cells. In: Journal of Leukocyte Biology. 2012 ; Vol. 92, No. 5. pp. 987-997.
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