PD1单抗临床应用归纳PPT课件

复杂的肿瘤：免疫系统T细胞转运至肿瘤(CTLs)Trafficking of启动和激活(APCs和T细胞)T cells to tumorsPriming and activationT细胞浸润进肿瘤Anti-CTLA4Anti-CD137(agonist)Anti-OX40(agonist)Anti-CD27(agonist)1L-2bloodIL-12Infiltration of T cellsvesselinto tumorsAnti-VEGF肿瘤抗原提呈lymph nodeT细胞识别肿瘤细胞Cancer antigenpresentationVaccinesIFN-aRecognition ofGM-CSFcancer cells by T cellsAnti-CD40 (agonist)TLR agonistsCARs杀灭肿瘤细胞肿瘤细胞抗原释放Killing of cancer cells(肿瘤细胞)Anti-PD-L1Release ofAnti-PD-1cancer cell antigensIDO inhibitors传统治疗锦上添花ChemotherapyRadiation therapyTargeted therapyCheckpoint抑制剂开疆辟土Chen DS,Mellman I.Immunity.2013.25:39(1):1-10.肿瘤通过多种机制发生免疫逃逸Tumor,肿瘤抗原表达下调cellIFNy-mediatedupregulation ofPD-L1/PD-1-与免疫细胞Cross-talk导致微tumor PD-L1mediated inhibitionPDL1oftumor cell killing环境中的免疫抑制增强recepPD.1ILBZHT71IFNShp-2/Priming andTCRactivation of T cells免疫抑制性细胞因子水平升高P13KPDL1 B7.1NFKB3hp-Dendritic免疫检查点蛋白(checkpointP0-1P0L1cellCD8+CytotoxicT Lymphocyte日7.1(CTL)PD-L1protein)过表达，如PD-l/PDPD-1/PD-1PD-L1PD-L1T-cellPD-L1cellPolartzationLlImmune cellTumor-modulation of TassociatedcellsfibroblastPD-L2 PD-1M2TH-2TcellmacrophageStromal PD-L1modulation of T cells平儿-413PD-L2-mediatedinhibition of TH,T cellsChen DS,Mellman I.Immunity.2013.20Chen DS,et al.Clin Cancer Res.2012:18(24):6580-7