NEJM:黑色素瘤患者PD-1免疫疗法耐药性的机制被揭示

2016-07-15 MedSci MedSci原创

黑色瘤患者接受抗程序性死亡1(PD-1)治疗时的客观反应率约为75%,耐受性良好,效果可持续数年,但是首次用药后仍会出现延迟复发,尽管此时仍在使用抗PD-1治疗。而这种免疫逃避机制尚未可知。研究人员分析了4名转移性黑色素瘤患者基线及复发病损区域的活组织检查样本。这4名患者初次接受抗PD-1治疗(pembrolizumab)后肿瘤消退,但是日后肿瘤复发数月至数年。测定获得性耐药肿瘤细胞的全基因组序列

黑色瘤患者接受抗程序性死亡1(PD-1)治疗时的客观反应率约为75%,耐受性良好,效果可持续数年,但是首次用药后仍会出现延迟复发,尽管此时仍在使用抗PD-1治疗。而这种免疫逃避机制尚未可知。



研究人员分析了4名转移性黑色素瘤患者基线及复发病损区域的活组织检查样本。这4名患者初次接受抗PD-1治疗(pembrolizumab)后肿瘤消退,但是日后肿瘤复发数月至数年。

测定获得性耐药肿瘤细胞的全基因组序列,结果发现,其中两名患者的肿瘤细胞的基因编码干扰素受体相关的Janus激酶1基因(JAK1)或Janus激酶2(JAK2)出现耐药相关的功能丧失突变,同时野生型等位基因缺失。第三名患者的基因编码抗原提呈蛋白β2-微球蛋白(B2M)出现了截短突变。JAK1和JAK2截短突变导致机体对干扰素γ反应缺失,包括对癌细胞的抗增殖作用不敏感。B2M截短突变导致主要组织相容性复合体I类的表明表达的缺失。

总而言之,该研究结果表明,黑色素瘤患者对PD-1免疫疗法耐药与参与干扰素受体信号途径和抗原呈递通路存在缺陷有关。

小知识:T细胞活化与抑制受体


原始出处:

Jesse M. Zaretsky, Angel Garcia-Diaz, et al., Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. July 13, 2016DOI: 10.1056/NEJMoa1604958.

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    2017-05-23 sunylz
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    2016-07-20 jetleo

    黑色素瘤患者对PD-1免疫疗法耐药与参与干扰素受体信号途径和抗原呈递通路存在缺陷有关。

    0

  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Mon Jul 18 22:30:00 CST 2016, time=2016-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558751, encodeId=d3041558e51a0, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sun Jul 17 11:51:00 CST 2016, time=2016-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564760, encodeId=a3a71564e6080, content=<a href='/topic/show?id=e27610332666' target=_blank 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level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eocJY6moGTnYzC8V8lUl3k679Uxh0PVMjIamhoDYuSYr6D4KDKlbpuNuCKFlJaiaVrmFIrbseIWqUA/132, createdBy=ad571630249, createdName=马里奥8433, createdTime=Sat Jul 16 10:04:00 CST 2016, time=2016-07-16, status=1, ipAttribution=)]
    2016-07-18 doctorJiangchao

    值得大家去好好阅读

    0

  5. 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level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eocJY6moGTnYzC8V8lUl3k679Uxh0PVMjIamhoDYuSYr6D4KDKlbpuNuCKFlJaiaVrmFIrbseIWqUA/132, createdBy=ad571630249, createdName=马里奥8433, createdTime=Sat Jul 16 10:04:00 CST 2016, time=2016-07-16, status=1, ipAttribution=)]
    2016-07-18 doctorJiangchao

    好文章

    0

  6. 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level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eocJY6moGTnYzC8V8lUl3k679Uxh0PVMjIamhoDYuSYr6D4KDKlbpuNuCKFlJaiaVrmFIrbseIWqUA/132, createdBy=ad571630249, createdName=马里奥8433, createdTime=Sat Jul 16 10:04:00 CST 2016, time=2016-07-16, status=1, ipAttribution=)]
    2016-07-18 doctorJiangchao

    机制的创新

    0

  7. 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  8. 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  9. 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level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eocJY6moGTnYzC8V8lUl3k679Uxh0PVMjIamhoDYuSYr6D4KDKlbpuNuCKFlJaiaVrmFIrbseIWqUA/132, createdBy=ad571630249, createdName=马里奥8433, createdTime=Sat Jul 16 10:04:00 CST 2016, time=2016-07-16, status=1, ipAttribution=)]
    2016-07-16 xiaotaiyang1

    重要发现,学习了

    0

  10. 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createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Mon Jul 18 22:30:00 CST 2016, time=2016-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558751, encodeId=d3041558e51a0, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sun Jul 17 11:51:00 CST 2016, time=2016-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564760, encodeId=a3a71564e6080, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Sun Jul 17 11:51:00 CST 2016, time=2016-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=93192, encodeId=028c93192cc, content=重要发现,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Sat Jul 16 16:14:00 CST 2016, time=2016-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=93175, encodeId=cb24931e591, content=很重要的文章 可以通过机制反推 功课么, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eocJY6moGTnYzC8V8lUl3k679Uxh0PVMjIamhoDYuSYr6D4KDKlbpuNuCKFlJaiaVrmFIrbseIWqUA/132, createdBy=ad571630249, createdName=马里奥8433, createdTime=Sat Jul 16 10:04:00 CST 2016, time=2016-07-16, status=1, ipAttribution=)]
    2016-07-16 马里奥8433

    很重要的文章 可以通过机制反推 功课么

    0

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