REVIEWOpenAccessFerroptosis,necroptosis,andpyroptosisinanticancerimmunityRongTang1,2,3,4†,JinXu1,2,3,4†,BoZhang1,2,3,4†,JiangLiu1,2,3,4,ChenLiang1,2,3,4,JieHua1,2,3,4,QingcaiMeng1,2,3,4,XianjunYu1,2,3,4*andSiShi1,2,3,4*AbstractInrecentyears,cancerimmunotherapybasedonimmunecheckpointinhibitors(ICIs)hasachievedconsiderablesuccessintheclinic.However,ICIsaresignificantlylimitedbythefactthatonlyonethirdofpatientswithmosttypesofcancerrespondtotheseagents.Theinductionofcelldeathmechanismsotherthanapoptosishasgraduallyemergedasanewcancertreatmentstrategybecausemosttumorsharborinnateresistancetoapoptosis.However,todate,thepossibilityofcombiningthesetwomodalitieshasnotbeendiscussedsystematically.Recently,afewstudiesrevealedcrosstalkbetweendistinctcelldeathmechanismsandantitumorimmunity.Theinductionofpyroptosis,ferroptosis,andnecroptosiscombinedwithICIsshowedsynergisticallyenhancedantitumoractivity,eveninICI-resistanttumors.Immunotherapy-activatedCD8+Tcellsaretraditionallybelievedtoinducetumorcelldeathviathefollowingtwomainpathways:(i)perforin-granzymeand(ii)Fas-FasL.However,recentstudiesidentifiedanewmechanismbywhichCD8+Tcellssuppresstumorgrowthbyinducingferroptosisandpyroptosis,whichprovokedareviewoftherelationshipbetweentumorcelldeathmechanismsandimmunesystemactivation.Hence,inthisreview,wesummarizeknowledgeofthereciprocalinteractionbetweenantitumorimmunityanddistinctcelldeathmechanisms,particularlynecroptosis,ferroptosis,andpyroptosis,whicharethethreepotentiallynovelmechanismsofimmunogeniccelldeath.Becausemostevidenceisderivedfromstudiesusinganimalandcellmodels,wealsoreviewedrelatedbioinformaticsdataavailableforhumantissuesinpublicdatabases,whichpartiallyconfirmedthepresenceofinteractionsbetweentumorcelldeathandtheactivationofantitumorimmunity.Keywords:Necroptosis,Ferroptosis,Pyroptosis,AnticancerimmunityIntroductionThemechanismbywhichthehostimmunesystemrec-ognizesandkillstumorcellshasnotbeenwellestab-lished.Whetherdeadtumorcellshaveimmunogenicpotentialtoeliciteffect...
