ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewNKcellsshapepancreaticandoraltumormicroenvironments;roleininhibitionoftumorgrowthandmetastasisAnahidJewetta,b,⁎,JankoKosc,d,YumanFonge,f,Meng-WeiKoa,TahminehSafaeia,MilicaPerišićNanutc,KawaljitKauraaDivisionofOralBiologyandMedicine,TheJaneandJerryWeintraubCenterforReconstructiveBiotechnology,UCLASchoolofDentistry,LosAngeles,CA,USAbTheJonssonComprehensiveCancerCenter,UCLASchoolofDentistryandMedicine,LosAngeles,CA,USAcDepartmentofBiotechnology,JožefStefanInstitute,Ljubljana,SloveniadFacultyofPharmacy,UniversityofLjubljana,Ljubljana,SloveniaeDepartmentofSurgery,CityofHopeNationalMedicalCenter,Duarte,CA,USAfCenterofGeneTherapy,DepartmentofHematologyandHematopoieticCellTransplantation,BeckmanResearchInstitute,CityofHopeNationalMedicalCenter,Duarte,CA,USAARTICLEINFOKeywords:Naturalkiller(NK)cellsCancerstemcells(CSCs)DifferentiationCancerimmunotherapySuper-chargedNKcellsSonicatedAJ2Humanized-BLT(hu-BLT)miceIFN-γCytotoxicityABSTRACTWehaverecentlyshownthatnaturalkiller(NK)cellsselectanddifferentiatecancerstemcells(CSCs)/un-differentiatedtumorsviasecretedandmembraneboundIFN-gamma(IFN-γ)andTNF-alpha(TNF-α),preventingtumorgrowthandinducingremodelingofthetumormicroenvironment.Sincemanyconventionaltherapeuticstrategies,includingchemotherapyandradiotherapyremainfairlyunsuccessfulintreatingCSCs/poorlydif-ferentiatedtumors,therehasbeenanincreasinginterestinNKcell-targetedimmunotherapyforthetreatmentofaggressivetumors.Inourrecentstudies,weusedhumanized-BLT(hu-BLT)mousemodelwithtransplantedhumanbonemarrow,liverandthymustodemonstratetheefficacyofadoptivetransferofexvivoexpanded,super-chargedNKcellsinselectionanddifferentiationofstem-liketumorswithinthecontextofafullyrecon-stitutedhumanimmunesystem.Furthermore,wehavedemonstratedthatCSCsdifferentiatedwithsplit-aner-gizedNKcellspriortoimplantationinhu-BLTmicewerenotabletogrowormetastasize.However,whenNKcell-mediated...
