肺癌免疫治疗进展方法技巧.pptxVIP

肺癌免疫治疗进展Cancer Immunotherapy1Update of checkpoint Inhibitors in lung cancer therapy2Future Outlook3 OutlineCancer Immunotherapy1Update of checkpoint Inhibitors in lung cancer therapy2Future Outlook3 Outline靶向治疗人类抗击肿瘤的历史肿瘤免疫治疗具有特异性和靶向性，一直为临床医师高度关注，近年进步显著，使得免疫治疗成为更具期待的领域进入21世纪，分子靶向治疗如火如荼肿瘤免疫治疗—攻克肿瘤的新希望eSkepticism phase1986-1992Renaissance phase1997-Enthusiasm phase1976 1st checkpoint inhibitor approved for CA1990s Discovery of role of checkpoints in CA1997 1st mAB approved for CA1985 1st study with adoptive T-ce ll transfer in CA1976 1st study with BCG in bladder CA1890s 1st CA vaccine developed(coley)2010 1st cellular immunotherapy approved for CA1992 Il-2(Cytokine) approved for CA1986 IFNα(cytokine) approved for CA2014 2nd checkpoint inhibitor approved for CA1973 discovery of the dendritic cell(steinman)1978 Discovery of tumor specific mABsKey events in the history of cancer immunotherapy美国《Science》杂志:2013年六大值得关注的科学领域单细胞测序“普朗克”探测微波背景辐射人类连接组计划探索南极冰下世界癌症免疫疗法基础植物研究Breakthrough of year 2013Science. 2013 Dec 20;342(6165):1432-3Stimulatory and Inhibitory Factors in the Cancer-Immunity CycleImmunity. 39(1)25 July 2013, Pages 1–10CTLA-4 and PD-1/PD-L1 Checkpoint Blockade for Cancer Treatment Immune checkpoint blockade includes agents targeting the negative regulators CTLA-4 and PD-1 CTLA-4 attenuates the early activation of naive and memory T cells in the lymph nodes Agents targeting CTLA-4 include ipilimumab and tremelimumab In contrast, PD-1 modulates the effector phase of T cell activity in peripheral tissues via interaction with PD-L1 and PD-L2 Agents targeting PD-1 include nivolumab and MK-3475 Agents targeting PD-L1 include MPDL3280A and MEDI4736Kyi C, et al. FEBS Lett. 2014;588:368-376Comparing CTLA-4 and PD-1CTLA-4PD-1Biological functionInhibitory receptorInhibitory receptorExpression onT cells at the time of initial response to antigen (activated CD8+ T cells)Activated T cells, B cells, NK cellsTILs in different tumor typesMajor roleR