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

[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...

[学科分类] 生理学

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