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Science: 保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

2017-03-10 Leo.C MedSci原创

免疫疗法癌症PD-L1
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T细胞CD28/B7信号通路的激活是针对PD-L1的靶向治疗的重要组成部分

Programmed death-ligand 1 (PD-L1)是机体调节T细胞免疫反应的开关。当体内T细胞免疫过强时，PD-L1会结合T细胞上的受体从而使T细胞失活和凋亡，达到平衡机体免疫的作用。癌症病人体内的T细胞处于失活的状态，针对PD-L1的靶向治疗，从而使体内T细胞保持抗癌活性成为一种新的癌症免疫疗法。制药巨头默克和辉瑞是研发针对PD-L1的靶向治疗行业领军代表。

在新一期的Science杂志中，有两篇报道阐述了T细胞CD28/B7信号通路在PD-L1的靶向治疗中起到至关重要的作用。除了T细胞上的受体（TCR）识别抗原以外，T细胞上CD28/B7信号通路的激活对于T细胞的分化增殖及反应也起到重要的促进作用。Enfu Hui及其同事证明，当PD-L1结合T细胞后，相对于T细胞识别抗原的受体（TCR），PD-L1信号通路激活后更倾向于减低或者阻止CD28/B7信号通路，从而降低T细胞的活性。此外在另一篇报道中，Alice O. Kamphorst及其同事证明即使是给予阻断PD-L1信号的靶向治疗之后，T细胞的复苏及增值依然依赖CD28/B7信号通路的激活。在对于肺癌病人的PD-L1靶向治疗之后，在血液中增值的T细胞也主要是CD28/B7阳性的T细胞。

这两篇报导，同时证明保持T细胞CD28/B7信号通路的激活针对PD-L1的靶向治疗具有重大意义。针对CD28/B7信号通路的联合疗法是开发下一步PD-L1的靶向治疗的新思路。

原始出处：
Enfu Hui, Jeanne Cheung, Jing Zhu et al. T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition. Science 09 Mar 2017:DOI: 10.1126/science.aaf1292
Alice O.Kamphorst, Andreas Wieland, Tahseen Nasti et al. Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent. Science 09 Mar 2017:DOI: 10.1126/science.aaf0683 

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    2017-03-12 smartjoy

    #PD-L1#

    0

  2. 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    2017-03-12 jichang

    #SCIE#

    0

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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178982, encodeId=72271e89827c, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:38 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178981, encodeId=2b411e8981bb, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:21 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178980, encodeId=52fd1e8980a7, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:07 CST 2017, time=2017-03-11, status=1, ipAttribution=)]
    2017-03-12 wgx310

    #信号通路#

    0

  4. 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objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:43 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178983, encodeId=062c1e898352, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:02 CST 2017, time=2017-03-11, status=1, 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    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  5. 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objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:43 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178983, encodeId=062c1e898352, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:02 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178982, encodeId=72271e89827c, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:38 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178981, encodeId=2b411e8981bb, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:21 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178980, encodeId=52fd1e8980a7, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:07 CST 2017, time=2017-03-11, status=1, ipAttribution=)]
    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  6. 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objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:43 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178983, encodeId=062c1e898352, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:02 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178982, encodeId=72271e89827c, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:38 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178981, encodeId=2b411e8981bb, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:21 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178980, encodeId=52fd1e8980a7, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:07 CST 2017, time=2017-03-11, status=1, ipAttribution=)]
    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  7. 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objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:43 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178983, encodeId=062c1e898352, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:02 CST 2017, time=2017-03-11, status=1, 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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:21 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178980, encodeId=52fd1e8980a7, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:07 CST 2017, time=2017-03-11, status=1, ipAttribution=)]
    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  8. 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objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:43 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178983, encodeId=062c1e898352, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:34:02 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178982, encodeId=72271e89827c, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:38 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178981, encodeId=2b411e8981bb, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:21 CST 2017, time=2017-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178980, encodeId=52fd1e8980a7, content=保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRrYOibkVibW9vAkCfb2F55aHjqMoqUVaF9fuXIMCxexawSOsicpbF7Ria7o54zPK65PodlkwhPrNhLhS/0, createdBy=12f71314239, createdName=ann y, createdTime=Sat Mar 11 05:33:07 CST 2017, time=2017-03-11, status=1, ipAttribution=)]
    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  9. 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    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

  10. 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    2017-03-11 ann y

    保持T细胞CD28/B7信号通路的激活对于针对PD-L1的靶向治疗具有重大意义

    0

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