腎癌信號(hào)通路及免疫治療進(jìn)展課件

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