ReviewARticlehttps://doi.org/10.1038/s41590-019-0561-41DepartmentofRadiationOncology,UniversityofNavarraClinic,Pamplona,Spain.2CentrodeInvestigaciónMédicaAplicada(CIMA),Pamplona,Spain.3IIGM–ItalianInstituteforGenomicMedicine,c/oIRCCSCandiolo,Turin,Italy.4CandioloCancerInstitute,FPO-IRCCS,Candiolo,Italy.5DivisionofRadiotherapyandImaging,TheInstituteofCancerResearch,London,UK.6TheRoyalMarsdenHospital/InstituteofCancerResearchNationalInstituteforHealthBiomedicalResearchCentre,London,UK.7CentrodeInvestigaciónBiomédicaenReddeCáncer(CIBERONC),Madrid,Spain.8NavarraInstituteforHealthResearch(IDISNA),Pamplona,Spain.9DepartmentofRadiationOncology,WeillCornellMedicalCollege,NewYork,NY,USA.10SandraandEdwardMeyerCancerCenter,NewYork,NY,USA.11CarylandIsraelEnglanderInstituteforPrecisionMedicine,WeillCornellMedicine,NewYork,NY,USA.12DepartmentofDermatology,YaleSchoolofMedicine,NewHaven,CT,USA.13UniversitédeParis,Paris,France.14Theseauthorscontributedequally:MariaEsperanzaRodriguez-Ruiz,IlioVitale.*e-mail:deadoc80@gmail.comRadiationtherapy(RT)isusedwithcurativeorpalliativeintentinmorethan50%ofcancerpatients.Traditionally,RThasbeenharnessedasasafemeanstodeliverionizingenergytomalignantcells,resultingintheirpermanentproliferativeinactiva-tion(cellularsenescence)ordemise1.ConsiderabletechnologicalprogresshasfosteredthewidespreaddisseminationofmodernRTvariantsthatenablesuperiorfractionationschedulesandunprec-edentedanatomicalprecision,resultinginimprovedtherapeuticoutcomesinanumberoflocalizedoncologicalsettings2.However,ithasalsobecomeclearthat—atleastinsomesituations—thetherapeuticefficacyofRTnotonlyreflectstheinhibitionofirra-diatedcancercells,butalsoinvolvestheinitiationorpotentiationofanadaptive,tumor-targetingimmuneresponsethatoperateslocallyandsystemicallytocontrolmetastaticlesions3.Suchadis-taleffect,commonlyknownas“abscopalresponse,”isthoughttooriginatefromtheabilityofRTtoincreasethelocalavailabilityofantigensexpressedbycancercellsandnotcoveredbycentraltoler-ance(...
