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Blood：PD-L1在ALK+间变性大细胞淋巴瘤中表达上调的分子机制

2019-06-03 QQ MedSci原创

PD-L1ALK间变性大细胞淋巴瘤免疫逃逸
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以PD1/PR-L1为基础的免疫疗法的成功强调了PD-L1在肿瘤进展中的重要作用，并提示我们急需通过深入了解PD-L1的表达调控机制，来开发新的方法以减弱PF-L1的功能。ALK阳性的间变性大细胞淋巴瘤（ALK+ ALCL）由于ALK活性下游多条成瘤信号通路组成性激活而表达较高水平的PD-L1，使其成为研究肿瘤细胞中与PD-L1上调相关的信号通路的一个很好的模型。研究人员通过CRISPR/Cas9

以PD1/PR-L1为基础的免疫疗法的成功强调了PD-L1在肿瘤进展中的重要作用，并提示我们急需通过深入了解PD-L1的表达调控机制，来开发新的方法以减弱PF-L1的功能。

ALK阳性的间变性大细胞淋巴瘤（ALK+ ALCL）由于ALK活性下游多条成瘤信号通路组成性激活而表达较高水平的PD-L1，使其成为研究肿瘤细胞中与PD-L1上调相关的信号通路的一个很好的模型。

研究人员通过CRISPR/Cas9文库筛选来研究ALK+ALCL中PD-L1调控所需的分子效应。研究人员发现PD-L1诱导依赖于STAT3的NPM-ALK癌蛋白活化，以及含有GRB2/SOS1的信号体，该信号体可激活MEK-ERK和PI3K-AKT信号通路。这些涉及STAT3和GRB2/SOS1的信号网络最终通过转录因子IRF4和BATF3作用于PD-L1基因增强子区域诱导PD-L1表达。

IRF4和BATF3对PD-L1上调至关重要，IRF4表达与原发性ALK+ ALCL组织中的PD-L1水平相关。当与PD-1阳性T细胞和NK细胞共培养时，靶向这些ALK+ ALCL中的成瘤信号通路可极大程度的抑制PD-L1介导肿瘤免疫逃逸的能力。

综上所述，本研究揭示了PD-L1上调表达的调控中心，加深了我们对驱动肿瘤免疫逃逸的分子回路的了解，并为改进免疫治疗干预策略提供新的方向。

原始出处：

Jing-Ping Zhang， et al. A novel model of controlling PD-L1 expression in ALK+ Anaplastic Large Cell Lymphoma revealed by CRISPR screening. Blood 2019 ：blood.2019001043； doi： https：//doi.org/10.1182/blood.2019001043

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    2019-08-13 tcm99hq

    #ALK+#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1779675, encodeId=b1931e79675de, content=<a href='/topic/show?id=f47023119c' target=_blank style='color:#2F92EE;'>#ALK+#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2311, encryptionId=f47023119c, topicName=ALK+)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74c2229, createdName=tcm99hq, createdTime=Tue Aug 13 01:32:00 CST 2019, time=2019-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702570, encodeId=42931e025702a, 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=86, 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=Fri Mar 27 22:32:00 CST 2020, time=2020-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1255002, encodeId=b8a3125500287, content=<a href='/topic/show?id=be71139214f' target=_blank style='color:#2F92EE;'>#PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, 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=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463678, encodeId=212d14636e832, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=)]
    2020-03-27 marlenexl

    #细胞淋巴瘤#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1779675, encodeId=b1931e79675de, content=<a href='/topic/show?id=f47023119c' target=_blank style='color:#2F92EE;'>#ALK+#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2311, encryptionId=f47023119c, topicName=ALK+)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74c2229, createdName=tcm99hq, createdTime=Tue Aug 13 01:32:00 CST 2019, time=2019-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702570, encodeId=42931e025702a, 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=86, 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=Fri Mar 27 22:32:00 CST 2020, time=2020-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1255002, encodeId=b8a3125500287, content=<a href='/topic/show?id=be71139214f' target=_blank style='color:#2F92EE;'>#PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, 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=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463678, encodeId=212d14636e832, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=)]
    2019-06-05 smartjoy

    #PD-L1#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1779675, encodeId=b1931e79675de, content=<a href='/topic/show?id=f47023119c' target=_blank style='color:#2F92EE;'>#ALK+#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2311, encryptionId=f47023119c, topicName=ALK+)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74c2229, createdName=tcm99hq, createdTime=Tue Aug 13 01:32:00 CST 2019, time=2019-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702570, encodeId=42931e025702a, 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=86, 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=Fri Mar 27 22:32:00 CST 2020, time=2020-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1255002, encodeId=b8a3125500287, content=<a href='/topic/show?id=be71139214f' target=_blank style='color:#2F92EE;'>#PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, 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=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463678, encodeId=212d14636e832, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Wed Jun 05 06:32:00 CST 2019, time=2019-06-05, status=1, ipAttribution=)]
    2019-06-05 huangdf

    #变性#

    0

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