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1、肺癌免疫治療進(jìn)展FutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123OutlineFutureOutlookUpdateofcheckpointInhibitorsinlungcancertherapyCancerImmunotherapy123Outline腫瘤免疫治療—攻克腫瘤的新希望人類(lèi)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(jìn)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(jìn)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(guó)《Science》雜志:2013年六大值得關(guān)注的科學(xué)領(lǐng)域單細(xì)胞測(cè)序“普朗克”探測(cè)微波背景輻射人類(lèi)連接組計(jì)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
