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

Granulocytic myeloid‐derived suppressor cells from tumorbearing mice inhibit the differentiation of iTreg. 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.