单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2014/12/18,#,肾癌信号通路及免疫治疗进展,虞巍,北京大学第一医院泌尿外科,肾癌信号通路及免疫治疗进展虞巍,1,Conti A et al.Biomed Res Int.(2013),Conti A et al.Biomed Res Int.,2,调控肿瘤血管生成的信号通路,VHL-HIF-VEGF,PI3K-Akt-mTOR,调控肿瘤血管生成的信号通路VHL-HIF-VEGF,3,VHL-HIF-VEGF,Campbell-Walsh Urology 10th ed,VHL-HIF-VEGFCampbell-Walsh Uro,4,Santoni M et al.Int J Cancer.(2014),Santoni M et al.Int J Cancer.,5,Buczek M et al.Biochim Biophys Acta.(2014),Buczek M et al.Biochim Biophy,6,PI3K-Akt-mTOR,Albiges L et al.Oncologist.(,2012),PI3K-Akt-mTORAlbiges L et al.,7,Dienstmann R et al.Mol Cancer Ther.(2014),Dienstmann R et al.Mol Cancer,8,How can we manage resistance,Adjusting,dose,combination,therapy,Switch to another targeted,therapy,Development of novel agents targeting,Houk BE et al.Cancer Chemother Pharmacol.(2010),How can we manage resistanceAd,9,肾癌的免疫治疗,IFN,IL-2,Vaccine,Santoni M et al.Int J Cancer.(2014),肾癌的免疫治疗IFNSantoni M et al.Int,10,Checkpoint inhibitor,Kyi C,et al.FEBS Lett.(2014),Checkpoint inhibitorKyi C,et,11,CTLA4,PD-1,T,细胞表达时间,抗原接触后,48h,抗原长期接触后产生,配体表达,由抗原提呈细胞表达,CD80(B7.1)/CD80(B7.2),肿瘤或炎性组织表达,PD-L1(B7-H1),抗原提成细胞表达,PD-L2(B7-DC),小鼠相关基因敲除,由于自身免疫反应,导致迅速死亡,由于自身免疫反应,导致慢性死亡,阻断后反应,抗肿瘤,T,细胞特异性弱,抗肿瘤,T,细胞特异性强,CTLA-4,与,PD-1,区别,CTLA4PD-1T细胞表达时间抗原接触后48h抗原长期接触,PD-1/PD-L1 blockade,in RCC,PD-1/PD-L1 blockade in RCC,13,PD-1,Thompson RH,et al.Clin Cancer Res.(2007),PD-1Thompson RH,et al.Clin C,14,Thompson RH,et al.Clin Cancer Res.(2007),Thompson RH,et al.Clin Cance,15,PD-L1,Thompson RH,et al.Cancer Res.(2006),PD-L1Thompson RH,et al.Cance,16,Jilaveanu LB et al.J Cancer.(2014),Jilaveanu LB et al.J Cancer.,17,肾癌信号通路及免疫治疗进展课件,18,肾癌信号通路及免疫治疗进展课件,19,肾癌信号通路及免疫治疗进展课件,20,primary,end point,:comparison,of PFS,to,assess whether a dose-response,relationship exists,.,Secondary,end points,:PFS,objective,response rate,(ORR),time to response,duration of response,overall,survival(OS,),and AE rate.,primary end point:comparison,21,肾癌信号通路及免疫治疗进展课件,22,肾癌信号通路及免疫治疗进展课件,23,肾癌信号通路及免疫治疗进展课件,24,肾癌信号通路及免疫治疗进展课件,25,肾癌信号通路及免疫治疗进展课件,26,肾癌信号通路及免疫治疗进展课件,27,肾癌信号通路及免疫治疗进展课件,28,肾癌信号通路及免疫治疗进展课件,29,肾癌信号通路及免疫治疗进展课件,30,Tripathi A,et al.BioDrugs.,(2014),Tripathi A,et al.BioDrugs.(,31,Philips GK,et al.Int Immunol.(2014),Philips GK,et al.Int Immunol,32,肾癌信号通路及免疫治疗进展课件,33,肾癌信号通路及免疫治疗进展课件,34,Cancer Immunotherapy,Ascierto PA,et al.J Transl Med.(2014),Cancer ImmunotherapyAscierto P,35,谢 谢！,谢 谢！,36,