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1、肺癌免疫治療進展FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123OutlineFutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline腫瘤免疫治療—攻克腫瘤的新希望人類抗擊腫瘤的歷史腫瘤免疫治療具有特異性和靶向性，一直為臨床醫(yī)師高度關(guān)注，近年進步顯著，使得免疫治療成為更
2、具期待的領(lǐng)域1896年coley毒素應(yīng)用于臨床1899年放療治愈第1例病人1946年氮芥治療淋巴瘤獲得成功免疫治療放療化療靶向治療進入21世紀(jì)，分子靶向治療如火如荼eKeyeventsinthehistoryofcancerimmunotherapy1890s1stCAvaccinedeveloped(coley)1973discoveryofthedendriticcell(steinman)19761ststudywithBCGinbladderCA1978Discoveryoftumorspeci
3、ficmABs19851ststudywithadoptiveT-celltransferinCA1986IFNα(cytokine)approvedforCA1990sDiscoveryofroleofcheckpointsinCA1992Il-2(Cytokine)approvedforCA19971stmABapprovedforCA20101stcellularimmunotherapyapprovedforCA20111stcheckpointinhibitorapprovedforCA201
4、42ndcheckpointinhibitorapprovedforCAEnthusiasmphase1976-1985Skepticismphase1986-1992Renaissancephase1997-美國《Science》雜志:2013年六大值得關(guān)注的科學(xué)領(lǐng)域單細胞測序“普朗克”探測微波背景輻射人類連接組計劃探索南極冰下世界癌癥免疫療法基礎(chǔ)植物研究Breakthroughofyear2013Science.2013Dec20;342(6165):1432-3Immunity.39(1)25Ju
5、ly2013,Pages1–10StimulatoryandInhibitoryFactorsintheCancer-ImmunityCycleCTLA-4andPD-1/PD-L1checkpoint blockadeforcancertreatmentCTLA-4andPD-1/PD-L1 CheckpointBlockadeforCancerTreatmentImmunecheckpointblockadeincludesagentstargetingthenegativeregulatorsCT
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
