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核因子-κB及干扰素调节因子3在抗肿瘤免疫中的作用.docx

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核因子-κB及干扰素调节因子3在抗肿瘤免疫中的作用 Abstract NF-κBandIRF3areimportanttranscriptionfactorsintheregulationoftumorimmunity.Theactivationofthesefactorsiscriticalfortheinitiationandmaintenanceofimmuneresponsesagainstcancer.NF-κBisakeyregulatorofpro-inflammatorycytokinesandchemokines,whileIRF3controlstheexpressionoftypeIinterferonsandotherimmune-relatedgenes.Inthisreview,wesummarizetherolesofNF-κBandIRF3inantitumorimmunityandthemechanismsthatcontroltheiractivity.Wealsodiscussthepotentialoftargetingthesefactorsasatherapeuticapproachtoenhancetheeffectivenessofcurrentcancertherapies. Introduction Cancerisaleadingcauseofdeathworldwide,anditsincidenceisexpectedtocontinuetoriseinthecomingyears.Immunotherapyhasemergedasapromisingstrategyforthetreatmentofcancer,harnessingthepoweroftheimmunesystemtorecognizeanddestroytumorcells.Thesuccessofimmunotherapyreliesontheactivationofimmunecells,suchasTcellsandnaturalkiller(NK)cells,andtheproductionofcytokinesandchemokinesthatorchestratetheimmuneresponse.Transcriptionfactorsplayacriticalroleintheregulationoftheseimmuneprocesses,andthedysregulationofthesefactorscancontributetotumorimmuneevasionandprogression. NF-κBintumorimmunity NF-κBisatranscriptionfactorthatplaysacentralroleintheregulationofimmuneresponses.Initsinactivestate,NF-κBissequesteredinthecytoplasmbyinhibitoryproteinscalledIκBs.Uponstimulationbypro-inflammatorycytokines,Toll-likereceptor(TLR)ligands,orothersignals,IκBsarephosphorylatedanddegraded,allowingNF-κBtotranslocatetothenucleusandactivategeneexpression.NF-κBcancontrolthetranscriptionofawiderangeofgenesinvolvedinpro-inflammatorycytokineproduction,cellsurvival,andcellproliferation. Inthecontextoftumorimmunity,NF-κBplaysadualrole.Ontheonehand,NF-κBactivationcanpromotetherecruitmentofimmunecellsandtheproductionofpro-inflammatorycytokinesandchemokines,whichcanhelptoeliminatetumorcells.Ontheotherhand,NF-κBactivationcanalsocontributetotumorgrowthandsurvivalbyinducingtheexpressionofgenesthatpromoteangiogenesis,cellproliferation,andcellsurv