Targeted STAT3 disruption in myeloid cells alters immunosuppressor cell abundance in a murine model of spontaneous medulloblastoma

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: myeloid‐;    derived suppressor cell;    STAT3;    immunosuppression;   

DOI  :  10.1189/jlb.1012531

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Althoughtheimmunesystemmayprovideearlyprotectionagainstcancer,tumorsmayexploitthehealingarmoftheimmunesystemtoenhancetheirgrowthandmetastasis.Forexample,myeloidderivedsuppressorcells(MDSCs)arethoughttopromotetumorgrowthbyseveralmechanisms,includingthesuppressionofTcellactivity.IthasbeensuggestedthatSTAT3activationinmyeloidcellsmodulatesmultipleaspectsofMDSCphysiology,includingtheirexpansionandactivity.Whereasmostanimalstudiesinvestigatingtumorimmunologyhaveusedtumorimplants,weusedtransgenicmice(Smo*)thatspontaneouslydevelopmedulloblastomabraintumorstoinvestigatethetemporalaccumulationofMDSCswithintumorsandhowmyeloidSTAT3disruptionaffectsMDSCandotherimmunecelltypes.WefounddistinctpopulationsofMDSCinmedulloblastomatumors,withahighprevalenceofCD11b+Ly6G+Ly6Clow/−cells,describedpreviouslybyothersasG‐MDSCs.Thesewerefoundearlyintumordevelopment,inpremalignantlesionslocatedonthesurfaceofthecerebellumof28‐day‐oldmice.Infullydevelopedtumors,pSTAT3wasfoundinthemajorityofthesecells.ConditionalSTAT3genedisruptioninmyeloidcellsresultedinanenhancedproinflammatoryphenotypeofmacrophagesinSmo*mice.Moreover,asignificantreductionintheabundanceofG‐MDSCsandTregswasobservedwithintumorsalongwithanincreasedpresenceofCD4+andCD8+cells.DespitethesealterationsinimmunecellsinducedbymyeloidSTAT3disruption,wefoundnoeffectontumorincidenceinSmo*micewiththisdeletion...

【 授权许可】

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