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Cancer Res:二甲双胍阻断MDSC的免疫抑制作用,在卵巢癌治疗中发挥作用

2018-02-17 佚名 生物探索

1月26日,一个中国科学家小组在Cancer Research上发表了题为“Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer”的论文。此前,尽管有大量研究证实,二甲双胍能够发挥抗肿瘤作用,但背后的机制

1月26日,一个中国科学家小组在Cancer Research上发表了题为“Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer”的论文。

此前,尽管有大量研究证实,二甲双胍能够发挥抗肿瘤作用,但背后的机制尚不清楚。而该研究调查了二甲双胍治疗是如何在卵巢癌患者中发挥作用的。

结果显示,二甲双胍治疗是通过下调卵巢癌患者中“单核和多核MDSC亚群”(MDSC:myeloid-derived suppressor cells,骨髓源抑制细胞)中CD39和CD73的表达和胞外酶活性(ectoenzymatic activity)来阻断MDSC的免疫抑制作用。

进一步研究发现,二甲双胍触发了AMPKα(AMP-activated protein kinaseα)的激活,随后抑制了HIF-1α(hypoxia-inducible factor-α)的表达。而HIF-1α对诱导MDSC中CD39/CD73的表达至关重要。

研究还证实,二甲双胍治疗与患卵巢癌的糖尿病患者“更长的总生存期”有关。分析显示,二甲双胍诱导了“循环CD39+CD73+MDSC出现率的下降”以及“循环CD8+T细胞抗肿瘤活性的增加”。

据研究人员介绍,MDSC是一群未成熟的骨髓细胞,可通过多种途径来抑制免疫系统,从而促进肿瘤的生长。功能性MDSC的积累已被证明是肿瘤诱导免疫抑制的主要“力量”。目前,许多靶向“MDSC诱导的免疫抑制”的疗法正处在临床开发中。

作者们在结论中总结道:该研究突出了二甲双胍对MDSC的直接作用;证明了在卵巢癌患者中,二甲双胍是通过抑制“CD39/CD73依赖性MDSC免疫抑制”,提高抗肿瘤T细胞免疫力,来产生临床益处的。

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    2020-07-21 lovetcm
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createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-12-11 hxj0125
  4. 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level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Fri Jun 29 22:18:00 CST 2018, time=2018-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=293061, encodeId=8b29293061be, content=****这么厉害?, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83erK1WhXxUtQFV7kmIyCaHlvuo3ABySzfwe1sPsXPYicXto30vXQ5ukZtKgpU9IkZ9HRRDzMMfYqwVQ/132, createdBy=19a82282835, createdName=guibaoliu, createdTime=Mon Mar 05 01:07:00 CST 2018, time=2018-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289101, encodeId=d289289101a3, content=学习了.获益匪浅!感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/0ed05bbc4eb124766d2a39104932ec4e.jpg, createdBy=5afd2091871, createdName=情途末路, createdTime=Mon Feb 19 07:40:32 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842791, encodeId=dd9d1842e91da, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Sun Jun 24 09:18:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288724, encodeId=2f74288e2460, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sat Feb 17 19:22:04 CST 2018, time=2018-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288661, encodeId=5dc628866121, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
  5. 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topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Tue Oct 23 00:18:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1647757, encodeId=2b84164e757f5, content=<a href='/topic/show?id=bc4d1142602' target=_blank style='color:#2F92EE;'>#MDSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11426, encryptionId=bc4d1142602, topicName=MDSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=057d23479763, createdName=hxj0125, createdTime=Tue Dec 11 01:18:00 CST 2018, time=2018-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635437, encodeId=8986163543ee8, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Fri Jun 29 22:18:00 CST 2018, time=2018-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=293061, encodeId=8b29293061be, content=****这么厉害?, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83erK1WhXxUtQFV7kmIyCaHlvuo3ABySzfwe1sPsXPYicXto30vXQ5ukZtKgpU9IkZ9HRRDzMMfYqwVQ/132, createdBy=19a82282835, createdName=guibaoliu, createdTime=Mon Mar 05 01:07:00 CST 2018, time=2018-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289101, encodeId=d289289101a3, content=学习了.获益匪浅!感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/0ed05bbc4eb124766d2a39104932ec4e.jpg, createdBy=5afd2091871, createdName=情途末路, createdTime=Mon Feb 19 07:40:32 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842791, encodeId=dd9d1842e91da, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Sun Jun 24 09:18:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288724, encodeId=2f74288e2460, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sat Feb 17 19:22:04 CST 2018, time=2018-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288661, encodeId=5dc628866121, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-03-05 guibaoliu

    ****这么厉害?

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=803604, encodeId=e06880360446, content=<a href='/topic/show?id=ce9d239823b' target=_blank style='color:#2F92EE;'>#二甲双胍#</a>神药, beContent=null, objectType=article, channel=null, level=null, likeNumber=189, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23982, encryptionId=ce9d239823b, topicName=二甲双胍)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Jul 21 00:30:40 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710119, encodeId=f16d1e101197e, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Tue Oct 23 00:18:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1647757, encodeId=2b84164e757f5, content=<a href='/topic/show?id=bc4d1142602' target=_blank style='color:#2F92EE;'>#MDSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11426, encryptionId=bc4d1142602, topicName=MDSC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=057d23479763, createdName=hxj0125, createdTime=Tue Dec 11 01:18:00 CST 2018, time=2018-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635437, encodeId=8986163543ee8, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/0ed05bbc4eb124766d2a39104932ec4e.jpg, createdBy=5afd2091871, createdName=情途末路, createdTime=Mon Feb 19 07:40:32 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842791, encodeId=dd9d1842e91da, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Sun Jun 24 09:18:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288724, encodeId=2f74288e2460, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sat Feb 17 19:22:04 CST 2018, time=2018-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288661, encodeId=5dc628866121, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-02-19 情途末路

    学习了.获益匪浅!感谢分享

    0

  7. 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beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/0ed05bbc4eb124766d2a39104932ec4e.jpg, createdBy=5afd2091871, createdName=情途末路, createdTime=Mon Feb 19 07:40:32 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842791, encodeId=dd9d1842e91da, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Sun Jun 24 09:18:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288724, encodeId=2f74288e2460, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sat Feb 17 19:22:04 CST 2018, time=2018-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288661, encodeId=5dc628866121, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-06-24 d830372
  8. 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GetPortalCommentsPageByObjectIdResponse(id=288724, encodeId=2f74288e2460, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sat Feb 17 19:22:04 CST 2018, time=2018-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288661, encodeId=5dc628866121, content=^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-02-17 131****1460

    学习了受益匪浅

    0

  9. 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createdTime=Sat Feb 17 10:48:04 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
    2018-02-17 wqkm

    ^_^^_^^_^

    0

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