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Blood：RS细胞中表达的PIM激酶如何影响霍奇金淋巴瘤细胞的免疫特性和存活？

2017-07-12 qinqiyun MedSci原创

RS细胞PIM激酶霍奇金淋巴瘤免疫逃逸治疗靶点
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典型霍奇金淋巴瘤（cHL）中的RS细胞表达多种免疫调节蛋白，形成cHL的微环境使得肿瘤细胞能够免疫逃逸。特定免疫调节蛋白的表达受促存活转录因子（如NFκB和STATs）调节。鉴于促存活转录因子还可以诱导致瘤性PIM1/2/3丝氨酸/苏氨酸激酶的表达，并且PIMs还能够调节NFκB和STATs的转录活性，Maciej Szydlowski及其同事猜测上述激酶有助于RS细胞存活和协助其免疫逃逸。研究人

典型霍奇金淋巴瘤（cHL）中的RS细胞表达多种免疫调节蛋白，形成cHL的微环境使得肿瘤细胞能够免疫逃逸。特定免疫调节蛋白的表达受促存活转录因子（如NFκB和STATs）调节。鉴于促存活转录因子还可以诱导致瘤性PIM1/2/3丝氨酸/苏氨酸激酶的表达，并且PIMs还能够调节NFκB和STATs的转录活性，Maciej Szydlowski及其同事猜测上述激酶有助于RS细胞存活和协助其免疫逃逸。研究人员研究PIM1/2/3在cHL内的表达情况并评估其在RS细胞免疫特性发展和存活过程中的作用。PIM1/2/3在原代和传代RS细胞中均有表达，其表达受NFκB和STATs活性调节。一种新开发的pan-PIM抑制剂，SEL24-B489，可使PIM发生基因性或化学性抑制，诱导RS细胞凋亡。抑制PIM可减少帽依赖蛋白转录、阻断JAK-STAT信号并显着下调NFκB依赖性基因的表达。在cHL移植瘤模型上，SEL24-B489延迟肿瘤生长达95.8%。而且，SEL24-B489可以减少与免疫抑制微环境形成相关的多种分子的表达，包括半乳凝素1和PD-L1/2。在共培养实验中，与用对照RS细胞孵化的T细胞相

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1789086, encodeId=37621e8908632, content=<a href='/topic/show?id=a3dd14290db' target=_blank style='color:#2F92EE;'>#PIM激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14290, encryptionId=a3dd14290db, topicName=PIM激酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Mon Mar 26 20:41:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1793514, encodeId=48d01e9351482, content=<a href='/topic/show?id=ed1015e1906' target=_blank style='color:#2F92EE;'>#RS细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15719, encryptionId=ed1015e1906, topicName=RS细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Fri Apr 13 12:41:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495973, encodeId=ebef14959e361, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Thu Jul 13 22:41:00 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221406, encodeId=fe2b221406b7, content=非常好的文章，学习了，很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Wed Jul 12 13:05:54 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2018-03-26 FukaiBao

    #PIM激酶#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1789086, encodeId=37621e8908632, content=<a href='/topic/show?id=a3dd14290db' target=_blank style='color:#2F92EE;'>#PIM激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14290, encryptionId=a3dd14290db, topicName=PIM激酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Mon Mar 26 20:41:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1793514, encodeId=48d01e9351482, content=<a href='/topic/show?id=ed1015e1906' target=_blank style='color:#2F92EE;'>#RS细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15719, encryptionId=ed1015e1906, topicName=RS细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Fri Apr 13 12:41:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495973, encodeId=ebef14959e361, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Thu Jul 13 22:41:00 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221406, encodeId=fe2b221406b7, content=非常好的文章，学习了，很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Wed Jul 12 13:05:54 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2018-04-13 bioon1

    #RS细胞#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1789086, encodeId=37621e8908632, content=<a href='/topic/show?id=a3dd14290db' target=_blank style='color:#2F92EE;'>#PIM激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14290, encryptionId=a3dd14290db, topicName=PIM激酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Mon Mar 26 20:41:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1793514, encodeId=48d01e9351482, content=<a href='/topic/show?id=ed1015e1906' target=_blank style='color:#2F92EE;'>#RS细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15719, encryptionId=ed1015e1906, topicName=RS细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Fri Apr 13 12:41:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495973, encodeId=ebef14959e361, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Thu Jul 13 22:41:00 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221406, encodeId=fe2b221406b7, content=非常好的文章，学习了，很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Wed Jul 12 13:05:54 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-07-13 redcrab

    #激酶#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1789086, encodeId=37621e8908632, content=<a href='/topic/show?id=a3dd14290db' target=_blank style='color:#2F92EE;'>#PIM激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14290, encryptionId=a3dd14290db, topicName=PIM激酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Mon Mar 26 20:41:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1793514, encodeId=48d01e9351482, content=<a href='/topic/show?id=ed1015e1906' target=_blank style='color:#2F92EE;'>#RS细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15719, encryptionId=ed1015e1906, topicName=RS细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Fri Apr 13 12:41:00 CST 2018, time=2018-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495973, encodeId=ebef14959e361, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Thu Jul 13 22:41:00 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221406, encodeId=fe2b221406b7, content=非常好的文章，学习了，很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Wed Jul 12 13:05:54 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-07-12 天涯183

    非常好的文章，学习了，很受益

    0