腎癌信號通路及免疫治療進展課件

腎癌信號通路及免疫治療進展腎癌信號通路及免疫治療進展1腎癌信號通路及免疫治療進展課件2調(diào)控腫瘤血管生成的信號通路VHL-HIF-VEGFPI3K-Akt-mTOR調(diào)控腫瘤血管生成的信號通路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腎癌的免疫治療IFNIL-2VaccineSantoniMetal.IntJCancer.(2014)腎癌的免疫治療IFNSantoniMetal.Int10CheckpointinhibitorKyiC,etal.FEBSLett.(2014)CheckpointinhibitorKyiC,et11CTLA4PD-1T細胞表達時間抗原接觸后48h抗原長期接觸后產(chǎn)生配體表達由抗原提呈細胞表達CD80(B7.1)/CD80(B7.2)腫瘤或炎性組織表達PD-L1(B7-H1)抗原提成細胞表達PD-L2(B7-DC)小鼠相關(guān)基因敲除由于自身免疫反應導致迅速死亡由于自身免疫反應導致慢性死亡阻斷后反應抗腫瘤T細胞特異性弱抗腫瘤T細胞特異性強CTLA-4與PD-1區(qū)別CTLA4PD-1T細胞表達時間抗原接觸后48h抗原長期接觸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腎癌信號通路及免疫治療進展課件18腎癌信號通路及免疫治療進展課件19腎癌信號通路及免疫治療進展課件20primaryendpoint:comparisonofPFStoassesswhetheradose-responserelationshipexists.Secondaryendpoints:PFS,objectiveresponserate(ORR),timetoresponse,durationofresponse,overallsurvival(OS),andAErate.primaryendpoint:comparison21腎癌信號通路及免疫治療進展課件22腎癌信號通路及免疫治療進展課件23腎癌信號通路及免疫治療進展課件24腎癌信號通路及免疫治療進展課件25腎癌信號通路及免疫治療進展課件26腎癌信號通路及免疫治療進展課件27腎癌信號通路及免疫治療進展課件28腎癌信號通路及免疫治療進展課件29腎癌信號通路及免疫治療進展課件30TripathiA,etal.BioDrugs.(2014)TripathiA,etal.BioDrugs.(31PhilipsGK,etal.IntImmunol.(2014)PhilipsGK,etal.IntImmunol32腎癌信號通路及免疫治療進展課件33腎癌信號通路及免疫治療進展課件34CancerImmunotherapyAsciertoPA,etal.JTranslMed.(2014)CancerImmunotherapyAsciertoP35謝謝！謝謝！36腎癌信號通路及免疫治療進展腎癌信號通路及免疫治療進展37腎癌信號通路及免疫治療進展課件38調(diào)控腫瘤血管生成的信號通路VHL-HIF-VEGFPI3K-Akt-mTOR調(diào)控腫瘤血管生成的信號通路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腎癌的免疫治療IFNIL-2VaccineSantoniMetal.IntJCancer.(2014)腎癌的免疫治療IFNSantoniMetal.Int46CheckpointinhibitorKyiC,etal.FEBSLett.(2014)CheckpointinhibitorKyiC,et47CTLA4PD-1T細胞表達時間抗原接觸后48h抗原長期接觸后產(chǎn)生配體表達由抗原提呈細胞表達CD80(B7.1)/CD80(B7.2)腫瘤或炎性組織表達PD-L1(B7-H1)抗原提成細胞表達PD-L2(B7-DC)小鼠相關(guān)基因敲除由于自身免疫反應導致迅速死亡由于自身免疫反應導致慢性死亡阻斷后反應抗腫瘤T細胞特異性弱抗腫瘤T細胞特異性強CTLA-4與PD-1區(qū)別CTLA4PD-1T細胞表達時間抗原接觸后48h抗原長期接觸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腎癌信號通路及免疫治療進展課件54腎癌信號通路及免疫治療進展課件55腎癌信號通路及免疫治療進展課件56primaryendpoint:comparisonofPFStoassesswhetheradose-responserelationshipexists.Secondaryendpoints:PFS,objectiveresponserate(ORR),timetoresponse,durationofresponse,overallsurvival(OS),andAErate.primaryendpoint:comparison57腎癌信號通路及免疫治療進展課件58腎癌信號通路及免疫治療進展課件59腎癌信號通路及免疫治療進展課件60腎癌信號通路及免疫治療進展課件61腎癌信號通路及免疫治療進展課件62腎癌信號通路及免疫治療進展課件63腎癌信號通路及免疫治療進展課件64腎癌信號通路及免疫治療進展課件65腎癌信號通路及免疫治療進展課件66TripathiA,etal.BioDrugs.(2014)TripathiA,etal.BioDru