CancerCellReviewCytosolicDNASensinginOrganismalTumorControlClaireVanpouille-Box,1SandraDemaria,1,2,3SilviaC.Formenti,1,2andLorenzoGalluzzi1,2,4,*1DepartmentofRadiationOncology,WeillCornellMedicalCollege,StichRadiationOncology,525East68thStreet,Box#169,NewYork,NY10065,USA2SandraandEdwardMeyerCancerCenter,NewYork,NY,USA3DepartmentofPathologyandLaboratoryMedicine,WeillCornellMedicalCollege,NewYork,NY,USA4Universite´ParisDescartes/ParisV,Paris,France*Correspondence:deadoc@vodafone.ithttps://doi.org/10.1016/j.ccell.2018.05.013Besidesconstitutingafirstlayerofdefenseagainstmicrobialchallenges,thedetectionofcytosolicDNAisfundamentalformammalianorganismstocontrolmalignanttransformationandtumorprogression.TheaccumulationofDNAinthecytoplasmcaninitiatetheproliferativeinactivation(viacellularsenescence)orelimination(viaregulatedcelldeath)ofneoplasticcellprecursors.Moreover,cytosolicDNAsensingisinti-matelyconnectedtothesecretionofcytokinesthatsupportinnateandadaptiveantitumorimmunity.Here,wediscussthemolecularmechanismswherebycytosolicDNAenablescell-intrinsicand-extrinsiconcosuppression,andtheirrelevanceforthedevelopmentofnoveltherapeuticapproachesthatreinstateanticancerimmunosurveillance.IntroductionAlongwithacquisitionofmulticellularity,evolvingeukaryotesdevelopedtheneedtopreserveorganismal(overcellular)ho-meostasis,ultimatelyresultinginarobustrewiringofadaptivestressresponses(Galluzzietal.,2018c).Mammaliancellsrespondtoperturbationsoftheintracellularorextracellularmicroenvironmentwithmechanismsthatinitiallyattempttorestorephysiologicalcellularfunctions(inthusfarresemblingunicellularorganisms).However,ifadaptationtostressfails,mammaliancellscanundergoeitheroftwoterminalfates:(1)cellularsenescence,correspondingtotheirirreversibleprolifera-tiveinactivation(Munoz-EspinandSerrano,2014);or(2)regu-latedcelldeath(RCD),viaeitherofmultiplenon-exclusiveandhighlyinterconnectedpathways(FuchsandSteller,2015;Gal-luzzietal.,2017c).BothsenescenceandRCDareinplaceforthemaintenanceoforganisma...
