ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewUnravelingthecrosstalkbetweenmelanomaandimmunecellsinthetumormicroenvironmentMonicaMarzagallia,NancyD.Ebeltb,EdwinR.Manuelb,⁎aDepartmentofPharmacologicalandBiomolecularSciences,UniversitàdegliStudidiMilano,Milano,ItalybDepartmentofImmuno-Oncology,BeckmanResearchInstituteofCityofHope,Duarte,California,USAARTICLEINFOKeywords:CutaneousmelanomaTumormicroenvironmentInnateandadaptiveimmunityImmunotherapyImmuneescapeSuppressionMetastasisCheckpointinhibitionCytokinetherapyVaccinationmicroRNAMetabolitesTregMDSCNKDCTcellsABSTRACTCutaneousmelanomaisthemostcommonskincancerwithanincidencethathasbeenrapidlyincreasinginthepastdecades.Melanomasareamongthemostimmunogenictumorsand,assuch,havethegreatestpotentialtorespondfavorablytoimmunotherapy.However,likemanycancers,melanomasacquirevarioussuppressivemechanisms,whichgenerallyactinconcert,toescapeinnateandadaptiveimmunedetectionanddestruction.Intenseresearchintothecellularandmoleculareventsassociatedwithmelanomagenesis,whichultimatelyleadtoimmunesuppression,hasresultedinthediscoveryofnewtherapeutictargetsandsynergisticcombinationsofimmunotherapy,targetedtherapyandchemotherapy.Tremendousefforttodetermineefficacyofsingleandcombinationtherapiesinpre-clinicalandclinicalphaseI-IIItrialshasledtoFDA-approvalofseveralim-munotherapeuticagentsthatcouldpotentiallybebeneficialforaggressive,highlyrefractory,advancedandmetastaticmelanomas.Theincreasingavailabilityofapprovedcombinationtherapiesformelanomaandmorerapidassessmentofpatienttumorshasincreasedthefeasibilityofpersonalizedtreatmenttoovercomepatientandtumorheterogeneityandtoachievegreaterclinicalbenefit.Here,wereviewtheevolutionoftheimmunesystemduringmelanomagenesis,mechanismsexploitedbymelanomatosuppressanti-tumorimmunityandmethodsthathavebeendevelopedtorestoreimmunity.Weemphasizethataneffectivetherapeuticstrategywillrequirecoordinateactivationoftumor-specificimmunityaswel...
