ArticleTumorExosomalRNAsPromoteLungPre-metastaticNicheFormationbyActivatingAlveolarEpithelialTLR3toRecruitNeutrophilsGraphicalAbstractHighlightsdTLR3deficiencyreduceslungmetastasisinthespontaneouscancermetastaticmodelsdHostTLR3promoteslungpre-metastaticnicheformationvianeutrophilrecruitmentdTumorexosomalRNAsactivatealveolarepithelialTLR3toinducechemokinesdHighTLR3levelandneutrophilinfiltrationinlungcancerpredictpoorprognosisAuthorsYanfangLiu,YanGu,YanmeiHan,...,XiaoqingXu,JianmingZheng,XuetaoCaoCorrespondencecaoxt@immunol.orgInBriefLiuetal.demonstratethatTLR3inhostalveolarepithelialcellsiscriticalforneutrophilrecruitmentandlungpre-metastaticnicheformation.Mechanistically,smallnuclearRNAsfromprimarytumor-derivedexosomesactivateTLR3,whichleadstochemokinesecretionandneutrophilinfiltration.AccessionNumbersGSE76397GSE80678Liuetal.,2016,CancerCell30,243–256August8,2016ª2016ElsevierInc.http://dx.doi.org/10.1016/j.ccell.2016.06.021CancerCellArticleTumorExosomalRNAsPromoteLungPre-metastaticNicheFormationbyActivatingAlveolarEpithelialTLR3toRecruitNeutrophilsYanfangLiu,1,4YanGu,1,4YanmeiHan,1QianZhang,1ZhengpingJiang,1XiangZhang,1BoHuang,2XiaoqingXu,2JianmingZheng,3andXuetaoCao1,2,*1NationalKeyLaboratoryofMedicalImmunology,InstituteofImmunology,SecondMilitaryMedicalUniversity,800XiangyinRoad,Shanghai200433,China2NationalKeyLaboratoryofMedicalMolecularBiology,DepartmentofImmunology,InstituteofBasicMedicalSciences,PekingUnionMedicalCollege,ChineseAcademyofMedicalSciences,Beijing100005,China3DepartmentofPathology,ChanghaiHospital,SecondMilitaryMedicalUniversity,Shanghai200433,China4Co-firstauthor*Correspondence:caoxt@immunol.orghttp://dx.doi.org/10.1016/j.ccell.2016.06.021SUMMARYThepre-metastaticnicheeducatedbyprimarytumor-derivedelementscontributestocancermetastasis.However,theroleofhoststromalcellsinmetastaticnicheformationandorgan-specificmetastatictropismisnotclearlydefined.Here,wedemonstratethatlungepithelialcellsarecriticalforinitiatingneutrophilrecruitmentandlungmetas...
