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CLIN CANCER RES：MDSC产生的一氧化氮损伤FcR介导的NK细胞功能

2018-04-27 MedSci MedSci原创

MDSCNK细胞一氧化氮
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单克隆抗体常用于治疗实体和血液学肿瘤，部分通过NK细胞的Fc受体（FcR）起作用。但是，肿瘤患者FcR介导的NK细胞功能显着受损。明确这一功能紊乱及抗体治疗反应受损机制有助于发展联合疗法增强抗体治疗效果。CLIN CANCER RES近期发表了一篇文章研究这一问题。

单克隆抗体常用于治疗实体和血液学肿瘤，部分通过NK细胞的Fc受体（FcR）起作用。但是，肿瘤患者FcR介导的NK细胞功能显着受损。明确这一功能紊乱及抗体治疗反应受损机制有助于发展联合疗法增强抗体治疗效果。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者使用肿瘤患者的自体NK细胞和髓源性抑制细胞（MDSC）研究MDSC对NK细胞FcR介导的包括抗体依赖细胞毒性，细胞因子产生和信号转导等功能的影响。使用鼠乳腺癌模型在体内研究MDSC对抗体治疗的影响以及探索单抗联合MDSC靶向药物联合治疗的效果。研究结果表明，肿瘤患者的MDSC可以抑制NK细胞FcR介导的抗体依赖细胞毒性，细胞因子产生和信号转导等功能。此外，胰腺癌鼠模型中输入MDSC会抵消单抗治疗的效果。抑制iNOS可以恢复NK细胞功能和信号转导。乳腺癌鼠模型汇中非特异性清除MDSC或抑制iNOS可以显着改善单抗治疗效果。

文章最后认为，MDSC会损伤FcR介导的NK细胞功能和信号转导，通过产生一氧化氮部分损伤单抗治疗反应。因此，清除MDSC或抑制一氧化氮产生为提高单抗治疗效果提供了新的策略。

原始出处：
Andrew Stiff,Parshant Trikha,et al.Nitric Oxide Production by Myeloid-Derived Suppressor Cells Plays a Role in Impairing FcReceptor-Mediated Natural Killer Cell Fucntion.CLIN CANCER RES.April 2018 doi:10.1158/1078-0432.CCR-17-0691

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    2018-10-22 hxj0125

    #MDSC#

    0

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    2018-10-04 d830372

    #MDS#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1647758, encodeId=b4db164e75867, content=<a href='/topic/show?id=bc4d1142602' target=_blank style='color:#2F92EE;'>#MDSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, 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=Mon Oct 22 16:06:00 CST 2018, time=2018-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842793, encodeId=d0361842e93c3, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 04 11:06:00 CST 2018, time=2018-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311173, encodeId=fe7e3111e3f1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Wed May 02 06:47:48 CST 2018, time=2018-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1337377, encodeId=794f133e37755, content=<a href='/topic/show?id=96fd19358fa' target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397527, encodeId=503a139e5279e, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586817, encodeId=c54a158681e41, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=)]
    2018-05-02 yfjms

    学习

    0

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    2018-04-29 ms7474195563676018

    #一氧化氮#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1647758, encodeId=b4db164e75867, content=<a href='/topic/show?id=bc4d1142602' target=_blank style='color:#2F92EE;'>#MDSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, 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=Mon Oct 22 16:06:00 CST 2018, time=2018-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842793, encodeId=d0361842e93c3, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 04 11:06:00 CST 2018, time=2018-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311173, encodeId=fe7e3111e3f1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Wed May 02 06:47:48 CST 2018, time=2018-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1337377, encodeId=794f133e37755, content=<a href='/topic/show?id=96fd19358fa' target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397527, encodeId=503a139e5279e, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586817, encodeId=c54a158681e41, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=)]
    2018-04-29 ms3046638856685384

    #损伤#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1647758, encodeId=b4db164e75867, content=<a href='/topic/show?id=bc4d1142602' target=_blank style='color:#2F92EE;'>#MDSC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, 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=Mon Oct 22 16:06:00 CST 2018, time=2018-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1842793, encodeId=d0361842e93c3, content=<a href='/topic/show?id=9f061142249' target=_blank style='color:#2F92EE;'>#MDS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11422, encryptionId=9f061142249, topicName=MDS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 04 11:06:00 CST 2018, time=2018-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311173, encodeId=fe7e3111e3f1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Wed May 02 06:47:48 CST 2018, time=2018-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1337377, encodeId=794f133e37755, content=<a href='/topic/show?id=96fd19358fa' target=_blank style='color:#2F92EE;'>#一氧化氮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19358, encryptionId=96fd19358fa, topicName=一氧化氮)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKjqGDO7icVKUiaT7urgwXvnvzWtp0fMFU46Xfib8oavFKygiaWtibXReS6ZUh3PImsNicGAwTO5HXxoicnA/132, createdBy=ee262500130, createdName=ms7474195563676018, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397527, encodeId=503a139e5279e, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586817, encodeId=c54a158681e41, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Sun Apr 29 04:06:00 CST 2018, time=2018-04-29, status=1, ipAttribution=)]
    2018-04-29 般若傻瓜

    #细胞功能#

    0

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