肿瘤科

订阅

MedSci主页 / 所有栏目 / 肿瘤科

JCI：Dinaciclib诱导免疫原性细胞死亡并增强PD-1抗体介导的肿瘤抑制

2018-02-26 MedSci MedSci原创

DinaciclibPD-1抗体免疫原性细胞死亡
关注

免疫检查点（PD-1）抑制剂已经在治疗癌症的临床上中显示出了巨大的成功，然而，大多数肿瘤对PD-1抗体的单一疗法具有抗性。许多正在进行的联合治疗研究揭示出PD-1抗体与其他治疗药物的相互补充可能产生更好的效果。

免疫检查点（PD-1）抑制剂已经在治疗癌症的临床上中显示出了巨大的成功，然而，大多数肿瘤对PD-1抗体的单一疗法具有抗性。许多正在进行的联合治疗研究揭示出PD-1抗体与其他治疗药物的相互补充可能产生更好的效果。

最近的研究发现免疫原性细胞死亡（ICD）能够改善不同肿瘤的T细胞应答，因此表明ICD可以进一步增强由PD-1抗体介导的抗肿瘤免疫性。在此，研究人员在免疫活性小鼠肿瘤模型中观察到PD-1抗体和细胞周期蛋白依赖性激酶抑制剂Dinaciclib的联合使用显示出了叠加的抗肿瘤活性。 Dinaciclib在肿瘤细胞内诱导了I型IFN基因的表达，导致Dinaciclib通过激发ICD来增强PD-1抗体的作用。事实上，用Dinaciclib治疗的肿瘤细胞显示出了多种ICD的特征，包括表面钙网蛋白的表达和高迁移率族蛋白1（HMGB1）和ATP的释放。用PD-1抗体和Dinaciclib治疗的小鼠在肿瘤内显示出了增加的T细胞浸润和DC激活，表明这种组合提高了免疫应答的总体质量。这些发现确定了Dinaciclib和PD-1抗体的联合应用的潜在机制，其中Dinaciclib能够诱导ICD，从而将肿瘤细胞转化为内源性疫苗并增强PD-1抗体的作用。 

原始出处：

Hossain, Dewan Md Sakib, et al. "Dinaciclib induces immunogenic cell death and enhances anti–PD-1–mediated tumor suppression." The Journal of clinical investigation 2018 128.2 doi:10.1172/JCI94586.

本文系梅斯医学（MedSci）原创编译整理，转载需授权!

版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1982099, encodeId=731a198209972, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Apr 30 02:30:00 CST 2018, time=2018-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809145, encodeId=ce61180914538, content=<a href='/topic/show?id=a68f829380b' target=_blank style='color:#2F92EE;'>#肿瘤抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82938, encryptionId=a68f829380b, topicName=肿瘤抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dcaa509, createdName=tsing_hit, createdTime=Wed May 23 10:30:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393796, encodeId=98d51393e96c6, content=<a href='/topic/show?id=718528982e3' target=_blank style='color:#2F92EE;'>#免疫原性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28982, encryptionId=718528982e3, topicName=免疫原性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577092, encodeId=ff2715e709268, content=<a href='/topic/show?id=a2a613914cd' target=_blank style='color:#2F92EE;'>#PD-1抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13914, encryptionId=a2a613914cd, topicName=PD-1抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=021d16387966, createdName=1249857fm37暂无昵称, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585870, encodeId=788815858e01c, content=<a href='/topic/show?id=60ca2898372' target=_blank style='color:#2F92EE;'>#免疫原性细胞死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28983, encryptionId=60ca2898372, topicName=免疫原性细胞死亡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=149c17305009, createdName=bioon9, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=)]
    2018-04-30 caobinglei8079

    #JCI#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1982099, encodeId=731a198209972, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Apr 30 02:30:00 CST 2018, time=2018-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809145, encodeId=ce61180914538, content=<a href='/topic/show?id=a68f829380b' target=_blank style='color:#2F92EE;'>#肿瘤抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82938, encryptionId=a68f829380b, topicName=肿瘤抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dcaa509, createdName=tsing_hit, createdTime=Wed May 23 10:30:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393796, encodeId=98d51393e96c6, content=<a href='/topic/show?id=718528982e3' target=_blank style='color:#2F92EE;'>#免疫原性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28982, encryptionId=718528982e3, topicName=免疫原性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577092, encodeId=ff2715e709268, content=<a href='/topic/show?id=a2a613914cd' target=_blank style='color:#2F92EE;'>#PD-1抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13914, encryptionId=a2a613914cd, topicName=PD-1抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=021d16387966, createdName=1249857fm37暂无昵称, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585870, encodeId=788815858e01c, content=<a href='/topic/show?id=60ca2898372' target=_blank style='color:#2F92EE;'>#免疫原性细胞死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28983, encryptionId=60ca2898372, topicName=免疫原性细胞死亡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=149c17305009, createdName=bioon9, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=)]
    2018-05-23 tsing_hit

    #肿瘤抑制#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1982099, encodeId=731a198209972, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Apr 30 02:30:00 CST 2018, time=2018-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809145, encodeId=ce61180914538, content=<a href='/topic/show?id=a68f829380b' target=_blank style='color:#2F92EE;'>#肿瘤抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82938, encryptionId=a68f829380b, topicName=肿瘤抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dcaa509, createdName=tsing_hit, createdTime=Wed May 23 10:30:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393796, encodeId=98d51393e96c6, content=<a href='/topic/show?id=718528982e3' target=_blank style='color:#2F92EE;'>#免疫原性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28982, encryptionId=718528982e3, topicName=免疫原性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577092, encodeId=ff2715e709268, content=<a href='/topic/show?id=a2a613914cd' target=_blank style='color:#2F92EE;'>#PD-1抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13914, encryptionId=a2a613914cd, topicName=PD-1抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=021d16387966, createdName=1249857fm37暂无昵称, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585870, encodeId=788815858e01c, content=<a href='/topic/show?id=60ca2898372' target=_blank style='color:#2F92EE;'>#免疫原性细胞死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28983, encryptionId=60ca2898372, topicName=免疫原性细胞死亡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=149c17305009, createdName=bioon9, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=)]
    2018-02-28 ms5353107019656438

    #免疫原性#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1982099, encodeId=731a198209972, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Apr 30 02:30:00 CST 2018, time=2018-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809145, encodeId=ce61180914538, content=<a href='/topic/show?id=a68f829380b' target=_blank style='color:#2F92EE;'>#肿瘤抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82938, encryptionId=a68f829380b, topicName=肿瘤抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dcaa509, createdName=tsing_hit, createdTime=Wed May 23 10:30:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393796, encodeId=98d51393e96c6, content=<a href='/topic/show?id=718528982e3' target=_blank style='color:#2F92EE;'>#免疫原性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28982, encryptionId=718528982e3, topicName=免疫原性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577092, encodeId=ff2715e709268, content=<a href='/topic/show?id=a2a613914cd' target=_blank style='color:#2F92EE;'>#PD-1抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13914, encryptionId=a2a613914cd, topicName=PD-1抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=021d16387966, createdName=1249857fm37暂无昵称, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585870, encodeId=788815858e01c, content=<a href='/topic/show?id=60ca2898372' target=_blank style='color:#2F92EE;'>#免疫原性细胞死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28983, encryptionId=60ca2898372, topicName=免疫原性细胞死亡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=149c17305009, createdName=bioon9, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=)]
    2018-02-28 1249857fm37暂无昵称

    #PD-1抗体#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1982099, encodeId=731a198209972, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Apr 30 02:30:00 CST 2018, time=2018-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809145, encodeId=ce61180914538, content=<a href='/topic/show?id=a68f829380b' target=_blank style='color:#2F92EE;'>#肿瘤抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82938, encryptionId=a68f829380b, topicName=肿瘤抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dcaa509, createdName=tsing_hit, createdTime=Wed May 23 10:30:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1393796, encodeId=98d51393e96c6, content=<a href='/topic/show?id=718528982e3' target=_blank style='color:#2F92EE;'>#免疫原性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28982, encryptionId=718528982e3, topicName=免疫原性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/78FA0899509C358B01B975E8EAC1F88A/100, createdBy=7d822500145, createdName=ms5353107019656438, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577092, encodeId=ff2715e709268, content=<a href='/topic/show?id=a2a613914cd' target=_blank style='color:#2F92EE;'>#PD-1抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13914, encryptionId=a2a613914cd, topicName=PD-1抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=021d16387966, createdName=1249857fm37暂无昵称, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585870, encodeId=788815858e01c, content=<a href='/topic/show?id=60ca2898372' target=_blank style='color:#2F92EE;'>#免疫原性细胞死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28983, encryptionId=60ca2898372, topicName=免疫原性细胞死亡)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=149c17305009, createdName=bioon9, createdTime=Wed Feb 28 11:30:00 CST 2018, time=2018-02-28, status=1, ipAttribution=)]
    2018-02-28 bioon9

    #免疫原性细胞死亡#

    0