ArticleMycCooperateswithRasbyProgrammingInflammationandImmuneSuppressionGraphicalAbstractHighlightsdMycandRascooperateinvivothroughthetumormicroenvironmentdMycdirectlyprogramsangiogenesis,inflammation,andimmunesuppressiondIL-23andCCL9arecellnon-autonomouseffectorsofMyc-drivenlungcarcinogenesisdMyc-driventumorgrowthandmaintenancedependonimmunesuppressionAuthorsRoderikM.Kortlever,NicoleM.Sodir,CatherineH.Wilson,...,LamornaBrownSwigart,TrevorD.Littlewood,GerardI.EvanCorrespondencegie20@cam.ac.ukInBriefOncogenicMycactivityorchestratesanimmunesuppressivetumormicroenvironment.Kortleveretal.,2017,Cell171,1301–1315November30,2017ª2017TheAuthors.PublishedbyElsevierInc.https://doi.org/10.1016/j.cell.2017.11.013ArticleMycCooperateswithRasbyProgrammingInflammationandImmuneSuppressionRoderikM.Kortlever,1,2NicoleM.Sodir,1,2CatherineH.Wilson,1DeborahL.Burkhart,1LucaPellegrinet,1LamornaBrownSwigart,2,3TrevorD.Littlewood,1andGerardI.Evan1,2,4,*1DepartmentofBiochemistry,UniversityofCambridge,80TennisCourtRoad,CambridgeCB21GA,UK2DepartmentofPathologyandHelenDillerFamilyComprehensiveCancerCenter,UniversityofCalifornia,SanFrancisco,SanFrancisco,CA94143,USA3Presentaddress:DepartmentofLaboratoryMedicine,UniversityofCalifornia,SanFrancisco,2340SutterStreet,SanFrancisco,CA94115,USA4LeadContact*Correspondence:gie20@cam.ac.ukhttps://doi.org/10.1016/j.cell.2017.11.013SUMMARYThetwooncogenesKRasandMyccooperatetodrivetumorigenesis,butthemechanismunderlyingthisremainsunclear.InamouselungmodelofKRasG12D-drivenadenomas,wefindthatco-activa-tionofMycdrivestheimmediatetransitiontohighlyproliferativeandinvasiveadenocarcinomasmarkedbyhighlyinflammatory,angiogenic,andimmune-suppressedstroma.Weidentifyepithelial-derivedsignalingmoleculesCCL9andIL-23astheprincipalinstructingsignalsforstromalreprogram-ming.CCL9mediatesrecruitmentofmacrophages,angiogenesis,andPD-L1-dependentexpulsionofTandBcells.IL-23orchestratesexclusionofadaptiveTandBcellsandinnateimmuneNKcells.Co-blockadeofbothCCL9andIL-23abrogatesMyc...
