肾癌信号通路及免疫治疗进展课件

肾癌信号通路及免疫治疗进展肾癌信号通路及免疫治疗进展1肾癌信号通路及免疫治疗进展课件2调控肿瘤血管生成的信号通路VHL-HIF-VEGFPI3K-Akt-mTOR调控肿瘤血管生成的信号通路VHL-HIF-VEGF3VHL-HIF-VEGFCampbell-WalshUrology10thedVHL-HIF-VEGFCampbell-WalshUro4SantoniMetal.IntJCancer.(2014)SantoniMetal.IntJCancer.5BuczekMetal.BiochimBiophysActa.(2014)BuczekMetal.BiochimBiophy6PI3K-Akt-mTORAlbigesLetal.Oncologist.(2012)PI3K-Akt-mTORAlbigesLetal.7DienstmannRetal.MolCancerTher.(2014)DienstmannRetal.MolCancer8HowcanwemanageresistanceAdjustingdosecombinationtherapySwitchtoanothertargetedtherapyDevelopmentofnovelagentstargetingHoukBEetal.CancerChemotherPharmacol.(2010)HowcanwemanageresistanceAd9肾癌的免疫治疗IFNIL-2VaccineSantoniMetal.IntJCancer.(2014)肾癌的免疫治疗IFNSantoniMetal.Int10CheckpointinhibitorKyiC,etal.FEBSLett.(2014)CheckpointinhibitorKyiC,et11CTLA4PD-1T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-L1blockadeinRCCPD-1/PD-L1blockadeinRCC13PD-1ThompsonRH,etal.ClinCancerRes.(2007)PD-1ThompsonRH,etal.ClinC14ThompsonRH,etal.ClinCancerRes.(2007)ThompsonRH,etal.ClinCance15PD-L1ThompsonRH,etal.CancerRes.(2006)PD-L1ThompsonRH,etal.Cance16JilaveanuLBetal.JCancer.(2014)JilaveanuLBetal.JCancer.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20primaryendpoint:comparisonofPFStoassesswhetheradose-responserelationshipexists.Secondaryendpoints:PFS,objectiveresponserate(ORR),timetoresponse,durationofresponse,overallsurvival(OS),andAErate.primaryendpoint:comparison21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30TripathiA,etal.BioDrugs.(2014)TripathiA,etal.BioDrugs.(31PhilipsGK,etal.IntImmunol.(2014)PhilipsGK,etal.IntImmunol32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34CancerImmunotherapyAsciertoPA,etal.JTranslMed.(2014)CancerImmunotherapyAsciertoP35谢谢！谢谢！36肾癌信号通路及免疫治疗进展肾癌信号通路及免疫治疗进展37肾癌信号通路及免疫治疗进展课件38调控肿瘤血管生成的信号通路VHL-HIF-VEGFPI3K-Akt-mTOR调控肿瘤血管生成的信号通路VHL-HIF-VEGF39VHL-HIF-VEGFCampbell-WalshUrology10thedVHL-HIF-VEGFCampbell-WalshUro40SantoniMetal.IntJCancer.(2014)SantoniMetal.IntJCancer.41BuczekMetal.BiochimBiophysActa.(2014)BuczekMetal.BiochimBiophy42PI3K-Akt-mTORAlbigesLetal.Oncologist.(2012)PI3K-Akt-mTORAlbigesLetal.43DienstmannRetal.MolCancerTher.(2014)DienstmannRetal.MolCancer44HowcanwemanageresistanceAdjustingdosecombinationtherapySwitchtoanothertargetedtherapyDevelopmentofnovelagentstargetingHoukBEetal.CancerChemotherPharmacol.(2010)HowcanwemanageresistanceAd45肾癌的免疫治疗IFNIL-2VaccineSantoniMetal.IntJCancer.(2014)肾癌的免疫治疗IFNSantoniMetal.Int46CheckpointinhibitorKyiC,etal.FEBSLett.(2014)CheckpointinhibitorKyiC,et47CTLA4PD-1T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-L1blockadeinRCCPD-1/PD-L1blockadeinRCC49PD-1ThompsonRH,etal.ClinCancerRes.(2007)PD-1ThompsonRH,etal.ClinC50ThompsonRH,etal.ClinCancerRes.(2007)ThompsonRH,etal.ClinCance51PD-L1ThompsonRH,etal.CancerRes.(2006)PD-L1ThompsonRH,etal.Cance52JilaveanuLBetal.JCancer.(2014)JilaveanuLBetal.JCancer.53肾癌信号通路及免疫治疗进展课件54肾癌信号通路及免疫治疗进展课件55肾癌信号通路及免疫治疗进展课件56primaryendpoint:comparisonofPFStoassesswhetheradose-responserelationshipexists.Secondaryendpoints:PFS,objectiveresponserate(ORR),timetoresponse,durationofresponse,overallsurvival(OS),andAErate.primaryendpoint:comparison57肾癌信号通路及免疫治疗进展课件58肾癌信号通路及免疫治疗进展课件59肾癌信号通路及免疫治疗进展课件60肾癌信号通路及免疫治疗进展课件61肾癌信号通路及免疫治疗进展课件62肾癌信号通路及免疫治疗进展课件63肾癌信号通路及免疫治疗进展课件64肾癌信号通路及免疫治疗进展课件65肾癌信号通路及免疫治疗进展课件66TripathiA,etal.BioDrugs.(2014)TripathiA,etal.BioDru