At the Bench: Preclinical rationale for CTLA‐4 and PD‐1 blockade as cancer immunotherapy

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

关键词: tumor;    receptor;    inhibitory;    coinhibitory;    costimulatory;    costimulation;    PD‐;    L1;    ipilimumab;   

DOI  :  10.1189/jlb.1212621

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Tumorscanavoidimmunesurveillancebystimulatingimmuneinhibitoryreceptorsthatfunctiontoturnoffestablishedimmuneresponses.ByblockingtheabilityoftumorstostimulateinhibitoryreceptorsonTcells,sustained,anti‐tumorimmuneresponsescanbegeneratedinanimals.Thus,therapeuticblockadeofimmuneinhibitorycheckpointsprovidesapotentialmethodtoboostanti‐tumorimmunity.TheCTLA‐4andPD‐1RsrepresenttwoTcell‐inhibitoryreceptorswithindependentmechanismsofaction.PreclinicalinvestigationsrevealedthatCTLA‐4enforcesanactivationthresholdandattenuatesproliferationoftumor‐specificTlymphocytes.Incontrast,PD‐1functionsprimarilyasastopsignalthatlimitsTcelleffectorfunctionwithinatumor.TheuniquemechanismsandsitesofactionofCTLA‐4andPD‐1suggestthatalthoughblockadeofeitherhasthepotentialtopromoteanti‐tumorimmuneresponses,combinedblockadeofbothmightofferevenmorepotentanti‐tumoractivity.SeerelatedreviewAttheBedside:CTLA‐4andPD‐1blockingantibodiesincancerimmunotherapy...

【 授权许可】

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