肺癌免疫治疗进展

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1、肺癌免疫治疗进展FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123OutlineFutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline肿瘤免疫治疗—攻克肿瘤的新希望人类抗击肿瘤的历史肿瘤免疫治疗具有特异性和靶向性，一直为临床医师高度关注，近年进步显著，使得免疫治疗成为更

2、具期待的领域1896年coley毒素应用于临床1899年放疗治愈第1例病人1946年氮芥治疗淋巴瘤获得成功免疫治疗放疗化疗靶向治疗进入21世纪，分子靶向治疗如火如荼eKeyeventsinthehistoryofcancerimmunotherapy1890s1stCAvaccinedeveloped(coley)1973discoveryofthedendriticcell(steinman)19761ststudywithBCGinbladderCA1978Discoveryoftumorspeci

3、ficmABs19851ststudywithadoptiveT-celltransferinCA1986IFNα(cytokine)approvedforCA1990sDiscoveryofroleofcheckpointsinCA1992Il-2(Cytokine)approvedforCA19971stmABapprovedforCA20101stcellularimmunotherapyapprovedforCA20111stcheckpointinhibitorapprovedforCA201

4、42ndcheckpointinhibitorapprovedforCAEnthusiasmphase1976-1985Skepticismphase1986-1992Renaissancephase1997-美国《Science》杂志:2013年六大值得关注的科学领域单细胞测序“普朗克”探测微波背景辐射人类连接组计划探索南极冰下世界癌症免疫疗法基础植物研究Breakthroughofyear2013Science.2013Dec20;342(6165):1432-3Immunity.39(1)25Ju

5、ly2013,Pages1–10StimulatoryandInhibitoryFactorsintheCancer-ImmunityCycleCTLA-4andPD-1/PD-L1checkpointblockadeforcancertreatmentCTLA-4andPD-1/PD-L1CheckpointBlockadeforCancerTreatmentImmunecheckpointblockadeincludesagentstargetingthenegativeregulatorsCT

6、LA-4andPD-1CTLA-4attenuatestheearlyactivationofnaiveandmemoryTcellsinthelymphnodesAgentstargetingCTLA-4includeipilimumabandtremelimumabIncontrast,PD-1modulatestheeffectorphaseofTcellactivityinperipheraltissuesviainteractionwithPD-L1andPD-L2Agentstargetin

7、gPD-1includenivolumabandMK-3475AgentstargetingPD-L1includeMPDL3280AandMEDI4736KyiC,etal.FEBSLett.2014;588:368-376ComparingCTLA-4andPD-1CTLA-4PD-1BiologicalfunctionInhibitoryreceptorInhibitoryreceptorExpressiononTcellsatthetimeofinitialresponsetoantigen(a

8、ctivatedCD8+Tcells)ActivatedTcells,Bcells,NKcellsTILsindifferenttumortypesMajorroleRegulatestheearlystageofT-cellactivationLimitsT-cellactivityinperipheraltissueafterinflammatoryresponseLimitsautoimmunityLigandsB7.1(CD80)B