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1、CancerCellArticleEndogenousTCellResponsestoAntigensExpressedinLungAdenocarcinomasDelayMalignantTumorProgressionMichelDuPage,1AnnF.Cheung,1ClaireMazumdar,1MonteM.Winslow,1RoderickBronson,2LeahM.Schmidt,1DeniseCrowley,1JianzhuChen,1andTylerJacks1,3,*1KochInstituteforIntegrativeCancerResearch
2、andDepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,MA02139,USA2DepartmentofBiomedicalSciences,TuftsCummingsSchoolofVeterinaryMedicine,NorthGrafton,MA01536,USA3HowardHughesMedicalInstitute,MassachusettsInstituteofTechnology,Cambridge,MA02139,USA*Correspondence:tjacks@mit.ed
3、uDOI10.1016/j.ccr.2010.11.011SUMMARYNeoantigensderivedfromsomaticmutationsintumorsmayprovideacriticallinkbetweentheadaptiveimmunesystemandcancer.Here,wedescribeasystemtointroduceexogenousantigensintogeneticallyengineeredmouselungcancerstomimictumorneoantigens.WeshowthatendogenousTcellsresp
4、ondtoandinfiltratetumors,significantlydelayingmalignantprogression.Despitecontinuedantigenexpression,Tcellinfiltrationdoesnotpersistandtumorsultimatelyescapeimmuneattack.Transplantationofcelllinesderivedfromtheselungtumorsorprophylacticvaccinationagainsttheautochthonoustumors,however,resultsi
5、nrapidtumoreradicationorselectionoftumorsthatloseantigenexpression.Theseresultsprovideinsightintothedynamicnatureoftheimmuneresponsetonaturallyarisingtumors.INTRODUCTIONHowever,thepersistenceofmalignantdiseasedespiteimmunerecognitionpresentsanimportantmedicalandtherapeuticThepotentialforfu
6、nctionallyimportantinteractionsbetweenquestion:howdotumorsescapeimmunesurveillance?adevelopingtumorandtheimmunesystemhasbeenappreci-Severalmousemodelshavebeenusedtogaininsightsintoatedforoveracentury.Theassociationoftumorcellsandthemechanismsbywhichtumorsmaysubvertimmunelymphocyteshasledre
7、searcherstopostulatethattheimmuneresponses,buteachofthesehascriticallimitations.Transplan-systemactivelyinhibitstheformationandprogressionoftrans-tationofprimaryorculturedtumorcellsiscommonlyused,butformedcellsandultimatelyshapesnascenttumorsbyforcingthesemode
