REVIEWOpenAccessExosome-mediatedcommunicationinthetumormicroenvironmentcontributestohepatocellularcarcinomadevelopmentandprogressionQinWu1,2,LingyunZhou1,2,DuoduoLv1,2,XiaZhu1,2andHongTang1,2*AbstractThetumormicroenvironment(TME)isanessentialintrinsicportionofhepatocellularcarcinoma(HCC)fortheregulationofitsorigination,development,invasion,andmetastasis.Asemergingcomponentsofthetumor-hostinteraction,exosomesareincreasinglyrecognizedasprofessionalcarriersofinformationinTMEandaspivotalmolecularentitiesinvolvedintumorigenicmicroenvironmentsetup.However,muchremainsunknownabouttheroleoftheexosomecommunicationsystemwithinTMEinthedevelopmentandprogressionofHCC.Inthisreview,wefocusontherolesandprobablemechanismsofTMEinHCCandshowtheexosome-basedimmuneregulationinTMEtopromoteHCC.MultipleprocessesareinvolvedinHCC,includingtumorsurvival,growth,angiogenesis,invasion,andmetastasis.WealsodiscussthespecificrolesofexosomesinHCCprocessesbymoldinghospitableTMEforHCC,suchasprovidingenergy,transmittingprotumorsignals,andevadinginhibitorysignals.Inaddition,exosomesinduceangiogenesisbychangingthebiologicalcharacteristicsofendothelialcellsanddirectlyregulatingproangiogenicandpropermeabilityfactors.Furthermore,exosomesmayleadtoHCCmetastaticinvasionbyepithelial-mesenchymaltransformation,extracellularmatrixdegradation,andvascularleakage.Finally,wesummarizethetherapeuticusageofexosomesintheHCCmicroenvironmentandattempttoprovideatheoreticalreferenceformodernantitumoragentsdesignedtotargetthesemechanisms.Keywords:Exosomes,Tumormicroenvironment,Hepatocellularcarcinoma,Immuneregulation,TherapyBackgroundThetumormicroenvironment(TME)isthecellularenvir-onmentinwhichthetumordevelops.Apartfromthetumorcells,theTMEincludesvariouscelltypes,extracel-lularmatrix(ECM),growthfactors,proteolyticenzymesandtheirinhibitors,andsignalingmolecules[1,2].TMEinfluencestumorgrowth,metastasis,andultimatelyprog-nosis.Therefore,thefundamentalroleofTMEistodynamicallyinteractwithmalignantcells[3].TheTMEcontributessignific...
