肾癌信号通路及免疫治疗进展课件

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,Conti A et al.Biomed Res Int.(2013),调控肿瘤血管生成的信号通路,VHL-HIF-VEGF,PI3K-Akt-mTOR,VHL-HIF-VEGF,Campbell-Walsh Urology 10th ed,Santoni M et al.Int J Cancer.(2014),Buczek M et al.Biochim Biophys Acta.(2014),PI3K-Akt-mTOR,Albiges L et al.Oncologist.(,2012),Dienstmann R et al.Mol Cancer Ther.(2014),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),肾癌的免疫治疗,IFN,IL-2,Vaccine,Santoni M et al.Int J Cancer.(2014),Checkpoint inhibitor,Kyi C,et al.FEBS Lett.(2014),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,PD-1/PD-L1 blockade,in RCC,PD-1,Thompson RH,et al.Clin Cancer Res.(2007),Thompson RH,et al.Clin Cancer Res.(2007),PD-L1,Thompson RH,et al.Cancer Res.(2006),Jilaveanu LB et al.J Cancer.(2014),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.,Tripathi A,et al.BioDrugs.,(2014),Philips GK,et al.Int Immunol.(2014),Cancer Immunotherapy,Ascierto PA,et al.J Transl Med.(2014),谢 谢！,