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Blood:在自然杀伤T细胞淋巴瘤中,STAT3信号通路激活可上调PD-L1的表达!

2018-08-01 MedSci MedSci原创

中心点:在PTCT和NKTL中,JAK/STAT信号通路常发生改变,其中STAT3和TP53是最常见的突变基因。在NKTL中,STAT3激活可促进PD-L1过表达,为STAT3抑制剂与免疫检查点抑制剂结合提供理论基础。摘要:成熟T细胞淋巴瘤,包括外周T细胞淋巴瘤(PTCL)和淋巴结外NK/T细胞淋巴瘤(NKTL),代表了一组异质性的非霍奇金淋巴瘤,治疗方案有限、预后差。为明确JAK/STAT信号通

中心点:

在PTCT和NKTL中,JAK/STAT信号通路常发生改变,其中STAT3和TP53是最常见的突变基因。

在NKTL中,STAT3激活可促进PD-L1过表达,为STAT3抑制剂与免疫检查点抑制剂结合提供理论基础。

摘要:

成熟T细胞淋巴瘤,包括外周T细胞淋巴瘤(PTCL)和淋巴结外NK/T细胞淋巴瘤(NKTL),代表了一组异质性的非霍奇金淋巴瘤,治疗方案有限、预后差。为明确JAK/STAT信号通路在该恶性肿瘤中的参与程度,Tammy Linlin Song等人对171位PTCL/NKTL患者该信号通路上的188个基因进行靶向捕获测序。

在73%的样本的101个基因上共发现了272个非自发性的体细胞突变,包括258个单核苷酸突变和14个插入或缺失突变。发生频率最高的突变位于STAT3和TP53(15%),其次是JAK3和JAK1(6%)和SOCS1(4%)。在NKTL中观察到一高发的特异性的STAT3突变(21%)。在缺乏细胞因子的情况下,新发STAT3突变(p.D427H、E616G、 p.E616K和p.E696K)可增加STAT3的磷酸化作用、增强STAT3的转录活性,而且其中p.E616K突变可通过将活化的STAT3结合至PD-L1基因的启动子,进而诱导PD-L1表达。

PD-L1在携带STAT3热点突变的NKTL细胞系中过表达,与上述结果一致;同样的,在STAT3野生型NKTL细胞系中过表达p.E616K和p.E616G可获得类似的现象。与之相反,沉默或抑制STAT3会降低STAT3突变型NKTL细胞系的PD-L1的表达。在NKTL肿瘤中,STAT3激活与PD-L1的表达明显相关。

综上所述,本研究证明了STAT3激活可上调PD-L1的表达,这可能是促进肿瘤细胞免疫逃逸的潜在机制。PD-1/PD-L1抗体与STAT3抑制剂结合或可提高NKTL,甚至是PTCL的治疗效果。

原始出处:

Tammy Linlin Song, et al. Oncogenic activation of STAT3 pathway drives PD-L1 expression in natural killer/T cell lymphoma. Blood  2018  :blood-2018-01-829424;  doi: https://doi.org/10.1182/blood-2018-01-829424

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    2018-08-03 smartjoy
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    2018-08-03 李研东
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    2018-08-02 kafei

    学习了谢谢

    0

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    2018-08-01 asuraxia

    学习了。

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1702502, encodeId=2f301e02502b5, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Mon Feb 25 11:45:00 CST 2019, time=2019-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1254962, encodeId=2cd01254962d3, content=<a href='/topic/show?id=be71139214f' target=_blank style='color:#2F92EE;'>#PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13921, encryptionId=be71139214f, topicName=PD-L1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Aug 03 01:45:00 CST 2018, time=2018-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348963, encodeId=f6371348963b5, content=<a href='/topic/show?id=684f16e52c8' target=_blank style='color:#2F92EE;'>#STAT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16752, encryptionId=684f16e52c8, topicName=STAT3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6e7948, createdName=李研东, createdTime=Fri Aug 03 01:45:00 CST 2018, time=2018-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372640, encodeId=e72013e2640f7, content=<a href='/topic/show?id=7d2d1802820' target=_blank style='color:#2F92EE;'>#T细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=132, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18028, encryptionId=7d2d1802820, topicName=T细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Fri Aug 03 01:45:00 CST 2018, time=2018-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539691, encodeId=2d3f153969150, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Fri Aug 03 01:45:00 CST 2018, time=2018-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=335716, encodeId=b16f335e165e, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Thu Aug 02 08:20:22 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=335554, encodeId=a7b433555406, content=学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=144, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2018/07/31/88b7a0fe36b7bac9361f6feb3f050afa.jpg, createdBy=674d2404499, createdName=asuraxia, createdTime=Wed Aug 01 15:04:49 CST 2018, time=2018-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=335542, encodeId=9a0233554237, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Wed Aug 01 13:33:17 CST 2018, time=2018-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=335521, encodeId=ef6633552171, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Wed Aug 01 12:04:46 CST 2018, time=2018-08-01, status=1, ipAttribution=)]
    2018-08-01 jihuaijun1112

    学习学习学习

    0

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    2018-08-01 sunfeifeiyang

    0

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