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: An Official Publication of the Reticuloendothelial Society

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 】

MDSCsandTregsplayanessentialroleintheimmunosuppressivenetworksthatcontributetotumor‐immuneevasion.Themechanismsbywhichtumorspromotetheexpansionand/orfunctionofthesesuppressivecellsandthecross‐talkbetweenMDSCandTregremainincompletelydefined.PreviousreportshavesuggestedthatMDSCmaycontributetoTreginductionincancer.Herein,weprovideevidencethattumor‐inducedgr‐MDSCs,endowedwiththepotentialofsuppressingconventionalTLc,surprisinglyimpairTGF‐β1‐mediatedgenerationofCD4+CD25+FoxP3+iTregs.Furthermore,gr‐MDSCsimpedetheproliferationofnTregswithout,however,affectingFoxP3expression.SuppressionofiTregdifferentiationfromnaïveCD4+cellsbygr‐MDSCoccursearlyinthepolarizationprocess,requiresinhibitionofearlyTcellactivation,anddependsonROSandIDObutdoesnotrequirearginase1,iNOS,NO,cystine/cysteinedepletion,PD‐1andPD‐L1signaling,orCOX‐2.Thesefindingsthusindicatethatgr‐MDSCsfromTBhostshavetheunanticipatedabilitytorestrictimmunosuppressiveTregs...

【 授权许可】

CC BY