Combinatorial approach to cancer immunotherapy: strength in numbers

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: immune checkpoints;    immunogenic cell death;    senescence;    melanoma;   

DOI  :  10.1189/jlb.5RI0116-013RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Immune‐checkpointblockadetherapywithantibodiestargetingCTLA‐4andPD‐1hasrevolutionizedmelanomatreatmentbyelicitingresponsesthatcanberemarkablydurableandisnowadvancingtoothermalignancies.However,notallpatientsrespondtoimmune‐checkpointinhibitors.Extensivepreclinicalevidencesuggeststhatcombiningimmune‐checkpointinhibitorswithotheranti‐cancertreatmentscangreatlyimprovethetherapeuticbenefit.Thefirstclinicalsuccessofthecombinatorialapproachtocancerimmunotherapywasdemonstratedusingadual‐checkpointblockadewithCTLA‐4andPD‐1inhibitors,whichresultedinacceleratedFDAapprovalofthistherapeuticregimen.Inthisreview,wediscussthecombinationsofcurrentandemergingimmunotherapeuticagentsinclinicalandpreclinicaldevelopmentandsummarizetheinsightsintopotentialmechanismsofsynergisticanti‐tumoractivitygainedfromanimalstudies.Thesepromisingcombinatorialpartnersfortheimmune‐checkpointblockadeincludetherapeuticstargetingadditionalinhibitoryreceptorsofTcells,suchasTIM‐3,LAG‐3,TIGIT,andBTLA,andagonistsofTcellcostimulatoryreceptors4‐1BB,OX40,andGITR,aswellasagentsthatpromotecancercellrecognitionbytheimmunesystem,suchastumorvaccines,IDOinhibitors,andagonistsoftheCD40receptorofAPCs.Wealsoreviewthetherapeuticpotentialofregimenscombiningtheimmune‐checkpointblockadewiththerapeuticinterventionsthathavebeenshowntoenhanceimmunogenicityofcancercells,includingoncolyticviruses,RT,epigenetictherapy,andsenescence‐inducingtherapy...

【 授权许可】

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