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

Journal of Leukocyte Biology

Jessica Kartchner¹  Sara M. Centuori, ⁵  Nona Janikashvili⁴  Bernard Bonnotte⁴  Darya Alizadeh⁵  Claire B. Larmonier¹  Malika Trad⁴  Collin J. LaCasse²  Emmanuel Katsanis, –³  Neale T. Hanke⁵  Nicolas Larmonier, –,,3 and³ 

[1] Department of Pediatrics, –BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;Department of Pediatrics, Department of Immunobiology, College of Medicine, –BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;Department of Pediatrics,  Cancer Biology Graduate Program, College of Medicine, Department of Immunobiology, College of Medicine, –BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;Faculty of Medicine, Dijon, and INSERM UMR 098, Besancon, France –BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;Department of Pediatrics,  Cancer Biology Graduate Program, College of Medicine, –BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA;

关键词: MDSC;    cancer;    immunosuppression;   

DOI  :  10.1189/jlb.0911465

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown