Combination of 4-1BB Agonist and PD-14Antagonist Promotes Antitumor EffectorMemory-1CD8 T Cells in a Poorly Immunogenic TumorBB激动剂与PD-1的联合应用 拮抗剂促进Antitumor Effector _记忆 免疫原性差的肿瘤中的CD8T细胞 模型

《Combination of 4-1BB Agonist and PD-14Antagonist Promotes Antitumor EffectorMemory-1CD8 T Cells in a Poorly Immunogenic TumorBB激动剂与PD-1的联合应用 拮抗剂促进Antitumor Effector _记忆 免疫原性差的肿瘤中的CD8T细胞 模型》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、PublishedOnlineFirstNovember11,2014;DOI:10.1158/2326-6066.CIR-14-0118ResearchArticleCancerImmunologyResearchCombinationof4-1BBAgonistandPD-1AntagonistPromotesAntitumorEffector/MemoryCD8TCellsinaPoorlyImmunogenicTumorModel112323ShihaoChen,Li-FenLee,TimothyS.Fisher,Bar

2、tJessen,MarkElliott,WinstonEvering,11212KathrynLogronio,GuangHuanTu,KonstantinosTsaparikos,XiaoaiLi,HuiWang,1121ChiYing,MengliXiong,ToddVanArsdale,andJohnC.LinAbstractImmunotherapiestargetingtheprogrammeddeath1(PD-1)PD-1cotreatment.Inthetumormicroenvironment,aneffect

3、ivecoinhibitoryreceptorhaveshowngreatpromiseforasubsetofantitumorimmuneresponsewasinducedasindicatedbytheþpatientswithcancer.However,robustandsafecombinationincreasedCD8/Tregratioandtheenrichmentofgenessuchastherapiesarestillneededtobringthebenefitofcancerimmuno-Cd3e,

4、Cd8a,Ifng,andEomes.Inthespleen,thecombinationtherapytobroaderpatientpopulations.Tosearchforanoptimaltreatmentshapedtheimmunesystemtoaneffector/memorystrategyofcombinatorialimmunotherapy,wehavecomparedthephenotypeandincreasedtheoverallactivityoftumor-specificþantitumor

5、activityoftheanti–4-1BB/anti–PD-1combinationCD8CTLs,reflectingalong-lastingsystemicantitumorresponse.withthatoftheanti–PD-1/anti–LAG-3combinationinthepoorlyFurthermore,combinationtreatmentinC57BL/6miceshowedimmunogenicB16F10melanomamodel.Pronouncedtumornoadditionalsaf

6、etysignals,andonlyminimallyincreasedsever-inhibitionoccurredonlyinanimalsreceivinganti–PD-1andityoftheknowntoxicityrelativeto4-1BBagonistalone.There-anti–4-1BBconcomitantly,whilecombininganti–PD-1withfore,intheabsenceofanycancervaccine,anti–4-1BB/anti–PD-1anti–LAG-3l

7、edtoamodestdegreeoftumorsuppression.Thecombinationtherapyissufficienttoelicitarobustantitumoractivityoftheanti–4-1BB/anti–PD-1combinationwasdepen-effector/memoryT-cellresponseinanaggressivetumormodelþdentonIFNgandCD8Tcells.Both4-1BBandPD-1proteinsandisthereforeacandid

8、ateforcombinationtrialsinpatients.þwereelevatedonthesurfaceofCD8Tcellsbyanti–4-1BB/anti–CancerImmunolRes;3(2);149–60.Ó2014AACR.Intr