樹突狀細胞與腫瘤免疫研究進展

DendritcCells.DevelopmentMyeloidDCPlasmacytoidDC#NATUREREVIEWS|IMMUNOLOGYVOLUME12|APRIL2012.DendriticcellsPresenceofdangersignalsAdaptiveimmunityAntigenpresentationInnateimmunityAbsenceofdangersignalsImmunetolerance.DendriticcellsPresenceofdangersignalsAdaptiveimmunityAntigenpresentationInnateimmunityAbsenceofdangersignalsImmunetolerance.AntigenpresentationKubyImmunology6thedition.EndogenousantigenKubyImmunology6thedition.ExogenousantigenMHCIIInvariantchainCLIP(ClassII-associatedInvariantChainPeptide)HLA－DM和HLA－DOKubyImmunology6thedition.ActivationofTcellSignal1Signal2CytokinesKubyImmunology6thedition.DendriticCellsNotonlyantigenpresentation!.DendriticcellsPresenceofdangersignalsAdaptiveimmunityAntigenpresentationInnateimmunityAbsenceofdangersignalsImmunetolerance.InduceinnateimmunityIMMUNOBIOLOGYOFDENDRITICCELLSJacquesBanchereauetal.Annu.Rev.Immunol.2000.18:767–811.DendriticcellsPresenceofdangersignalsAdaptiveimmunityAntigenpresentationInnateimmunityAbsenceofdangersignalsImmunetolerance.Immunetolerance#JournalofCancerMolecules2(6):213-215,2006..DendriticcellsPresenceofdangersignalsAdaptiveimmunityAntigenpresentationInnateimmunityAbsenceofdangersignalsImmunetolerance.TumormicroenvironmentandDCsHotIssue.Convertdifferent

DCstomacrophage-likeDCs#Immunol.2013Nov25;4:403.CD14+macrophage-likeDCsPoorTcellstimulatoryabililitesTcellsuppressiveactivityCalledM2-typemacrophagesCD1c#Immunol.2013Nov25;4:403.CD14+macrophage-likeDCsCD14+DDC(dermaldendriticcell)PoorinducersofallogeneicTcellsRequirehighDC:TcellratiosforTh1inductionCarrylowlevelsofco-stimulatorymolecules.Convertmonocytetomacrophage-likeDCsIL-10,IL-6,orPGE2#Blood.

2011November17;

118(20):5498–5505..Convertfullydifferentiated

DCstomacrophage-likeDCsIL-10#JInvestDermatol.2011Feb;131(2):418-25.doi:10.1038..Convertfullydifferentiated

DCstomacrophage-likeDCsIL-10#IntJGynecolCancer2009;19:1487Y1493.Convertfullydifferentiated

DCstomacrophage-likeDCsIL-10#IntJGynecolCancer2009;19:1487Y1493.Convertdifferent

DCstomacrophage-likeDCs#Immunol.2013Nov25;4:403.Macrophage-likeDCssharesomestrikingtraitsReleaseofimmunosuppressiveIL-10(high)ExpressionofHIF1a,TGF-β,VEGFA,MMP3,MMP9,IL-8,andTNFaContributetotumor-promotingprocessesEndothelialcellmigrationandproliferationTumorgrowthandinvasion.Changesthatoccurinmyeloidcellsincancer#NATUREREVIEWS|IMMUNOLOGYVOLUME12|APRIL2012.SIGNALTRANSDUCTIONPATHWAYSACTINGASMASTER

SWITCHESOFTUMOR-INDUCEDDCSUPPRESSION.JAK2/STAT3signalingpathway.JAK/STATsignalingpathwayActivatedbyinterferon,interleukin,growthfactorsJAK：JanusKinaseSTAT：Signaltransducersandactivatorsoftranscription#Science296(5573):1653–5.doi:10.1126/science.1071545.JAK2/STAT3signalingpathway#NatRevCancer.2009Nov;9(11):798-809.doi:10.1038/nrc2734INDIRECTEVIDENCE.CombinedSTAT3andp38-MAPK

inhibitionwasrequired#OncoImmunology1:5,649–658;august2012.CombinedSTAT3andp38-MAPK

inhibitionwasrequired#OncoImmunology1:5,649–658;august2012DIRECTEVIDENCE！.MonocyteImmatureDCMatureDCM2Macrophage-likeDCIL-10pSTAT3p38IL-10IL-6PEG2pSTAT3IL-10IL-6PEG2IL-10IL-10,HIF1a,TGF-β,VEGFA,MMP3,MMP9,IL-8,andTNFapSTAT3p38pSTAT3p38pSTAT3p38.THERAPEUTICACTIVATIONJAK2/STAT3and/orp38-MAPKsignalinginterferenceLocalimmunepotentiationDC-stimulatoryagentsGM-CSF,IL4.Localimmunepotentiation#BLOOD,12APRIL2012，VOLUME119,NUMBER15.LocalimmunepotentiationGM-CSF,IL4StimulateT,Bcells#JImmunol2012;189:5223-5229.LocalimmunepotentiationGM-CSF,IL4Moreantibody#JImmunol2012;189:5223-5229.LocalimmunepotentiationTLR

agonists,suchasLPSCpGoligodeoxynucleotides.MonocyteImmatureDCMatureDCM2Macrophage-likeDCIL-10pSTAT3p38IL-10IL-6PEG2pSTAT3IL-10IL-6PEG2IL-10IL-10,HIF1a,TGF-β,VEGFA,MMP3,MMP9,IL-8,andTNFapSTAT3p38pSTAT3p38pSTAT3p38.ReferencevandeVenR,LindenbergJJ,OosterhoffD,etal.DendriticCellPlasticityinTumor-ConditionedSkin:CD14+CellsattheCross-RoadsofImmuneActivationandSuppression[J].Frontiersinimmunology,2013,4.BanchereauJ,BriereF,CauxC,etal.Immunobiologyofdendriticcells[J].Annualreviewofimmunology,2000,18(1):767-811.LiuKJ.Dendriticcell,toll-likereceptor,andtheimmunesystem[J].JCancerMol,2006,2:213.ObermajerN,MuthuswamyR,LesnockJ,etal.PositivefeedbackbetweenPGE2andCOX2redirectsthedifferentiationofhumandendriticcellstowardstablemyeloid-derivedsuppressorcells[J].Blood,2011,118(20):5498-5505.OuwehandK,OosterhoffD,BreetveldM,etal.Irritant-inducedmigrationofLangerhanscellscoincideswithanIL-10-dependentswitchtoamacrophage-likephenotype[J].JournalofInvestigativeDermatology,2010,131(2):418-425..ChenF,HouM,YeF,LvW,XieX.Ovariancancercellsinduceperipheralmaturedendriticcellstodifferentiateintomacrophagelikecellsinvitro.IntJGynecolCancer(2009)19:1487–93.doi:10.1111/IGC.0b013e3181bb70c6YuH,PardollD,JoveR.STATsincancerinflammationandimmunity:aleadingroleforSTAT3[J].NatureReviewsCancer,2009,9(11):798-809.OosterhoffD,LougheedS,vandeVenR,etal.Tumor-mediatedinhibitionofhumandendriticcelldifferentiationandfunctionisconsistentlycounteractedbycombinedp38MAPKandSTAT3inhibition[J].Oncoimmunology,2012,1(5):649-658.VuylstekeRJCLM,MolenkampBG,vanLeeuwenPAM,MeijerS,WijnandsPGJTB,HaanenJBAG,etal.Tumor-speci?cCD8+TcellreactivityinthesentinellymphnodeofGM-CSF-treatedstageImelanomapatientsisassociatedwithhighmyeloiddendriticcellcontent.ClinCancerRes(2006)12:2826–33.doi:10.1158/1078-0432.CCR-05-2431.ChuC-C,AliN,KaragiannisP,DiMeglioP,SkoweraA,Napolitan