ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewTheroleofcancerstemcellsinthemodulationofanti-tumorimmuneresponsesCristinaMaccallia,⁎,KakilIbrahimRasulb,MamounElawadc,SoldanoFerronedaClinicalResearchCenter,TranslationalMedicine,SidraMedicine,Doha,QatarbHaemtologyandOncologyDepartment,NationalCenterforCancerCareandResearch(NCCCR),HamadMedicalCorporation,Doha,QatarcGastroenterology,HepatologyandNutritionDepartment,SidraMedicine,Doha,QatardDepartmentofSurgery,MassachusettsGeneralHospital,HarvardMedicalSchool,Boston,MA,USAARTICLEINFOKeywords:CancerstemcellsImmunologicalprofilingImmuneescapemechanismsTumordormancyImmune-basedinterventionsABSTRACTTumorlesionscomprisemultiplesubpopulationsofcellsincludingthoseendowedwith“stemness”properties.Thelattercellsareresponsibleoftumorinitiation,metastasisformation,resistancetoconventionaltherapiesanddiseaserecurrence.Theserelativelyrarecellsdenominatedcancerstemcells(CSCs)orcancerinitiatingcells(CICs)aredefinedbasedonself-renewing,multipotencyandtumorigenicity.Thesecellsthroughtheirim-munomodulatingfeaturescanevadefromimmunesurveillance,persistingintheformofquiescenceanddor-mancy.Theycandrivetheneoplasticgrowthandrecurrence,evenafterlonglatency.Moreover,CSCs/CICsduetotheirabilitytomodulateandshapeimmuneresponsescanrepresentthecomponentofatumorcausingimmunotherapyresistanceincancerpatients.InthisreviewageneraloverviewofimmunologicalpropertiesofCSCs/CICsisprovided,withaspecialfocusonthemechanismsofmodulationofTcellmediatedresponses.TheneedtofurtherdissectthemechanismsregulatingtheimmunologicalprofileofCSCs/CICsandtheirinteractionswithimmunecellsandtumormicroenvironmentisdiscussed.Animprovedcharacterizationoftheim-munologicalpropertiesofCSCs/CICswillcontributetotherationaledesignofimmunotherapeuticinterventionswhichtargetthesecellsandmayleadtotheeradicationofmalignantdiseases.1.IntroductionAsshownforthefirsttimebyThomasandBurnet(ThomasL.,Hoeber-Harper,1959NewYork...
