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Nat Commun:循环CD8+T细胞的染色质可及性预测胃癌患者对抗PD-1疗法的应答

2021-02-18 xiaozeng MedSci原创

关于持续性抗原刺激(如慢性病毒感染和肿瘤)引起的免疫细胞衰竭和肿瘤浸润淋巴细胞(TIL)功能障碍的研究显示,细胞表面蛋白与免疫细胞的功能受损有关。

关于持续性抗原刺激(如慢性病毒感染和肿瘤)引起的免疫细胞衰竭和肿瘤浸润淋巴细胞(TIL)功能障碍的研究显示,细胞表面蛋白与免疫细胞的功能受损有关。这些蛋白质包括多重共抑制因子或检查点受体,如CTLA-4(细胞毒性T淋巴细胞抗原4,CD152),PD-1(程序性死亡受体1,CD279),TIM-3(T细胞免疫球蛋白粘蛋白-3)和LAG-3(淋巴细胞活化基因3)。

因此,目前已开展采用针对免疫检查点(即免疫检查点抑制剂ICI)的中和抗体(Abs)以恢复T细胞功能的相关临床试验。这些ICI药物目前已被批准用于那些至少有两项系统性化学疗法失败的转移性胃癌(mGC)患者。


尽管肿瘤基因组分析已鉴定出一小部分胃癌(GC)患者可从抗PD-1治疗中受益,但并不是所有反应都可以单独通过肿瘤测序来解释。

以ATAC-seq为基础的分子诊断示意图

该研究通过定量评估患者外周血中循环CD8+T细胞的全基因组染色质可及性,旨在探究与抗PD-1治疗差异反应相关的表观遗传学因素。


通过ATAC-seq(结合高通量测序技术的靶向开放染色质的研究方法)技术,研究人员确定了染色质的独特开放区域,该区域能够显著区分抗PD-1治疗的应答者和非应答者。在应答者组中,循环CD8+T细胞染色质开放度较高的GC患者显著富集。相应地,在循环CD8+T细胞的特定基因组位置上具有高染色质开放性的患者,其生存率要显著高于染色质封闭性的患者。

循环CD8+T细胞染色质开放度与抗PD-1治疗应答的相关性

综上,该研究揭示了基线CD8+T细胞的表观遗传学特征可用于鉴定潜在的受益于抗PD-1治疗的转移性GC患者。


原始出处:

Shin, H.M., Kim, G., Kim, S. et al. Chromatin accessibility of circulating CD8+ T cells predicts treatment response to PD-1 blockade in patients with gastric cancer. Nat Commun 12, 975 (12 February 2021).

 

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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605411, encodeId=88981605411e4, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=925371, encodeId=e0339253e198, content=<a href='/topic/show?id=a4cb13896d3' target=_blank style='color:#2F92EE;'>#PD-1/PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=193, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13896, encryptionId=a4cb13896d3, topicName=PD-1/PD-L1)], attachment=null, 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  5. [GetPortalCommentsPageByObjectIdResponse(id=1884997, encodeId=4277188499ebf, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Apr 24 18:38:25 CST 2021, time=2021-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1051118, encodeId=fbc1105111870, content=<a href='/topic/show?id=fe74436549' target=_blank style='color:#2F92EE;'>#CD8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4365, encryptionId=fe74436549, topicName=CD8+T)], attachment=null, authenticateStatus=null, 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href='/topic/show?id=4b5c564252' target=_blank style='color:#2F92EE;'>#D8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5642, encryptionId=4b5c564252, topicName=D8+T)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Mon Oct 11 00:38:25 CST 2021, time=2021-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575950, encodeId=09d415e5950f8, content=<a href='/topic/show?id=dc0e6184243' target=_blank style='color:#2F92EE;'>#染色质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61842, encryptionId=dc0e6184243, topicName=染色质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d4ac16256960, createdName=guozhenyu, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605411, encodeId=88981605411e4, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=925371, encodeId=e0339253e198, content=<a href='/topic/show?id=a4cb13896d3' target=_blank style='color:#2F92EE;'>#PD-1/PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=193, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13896, encryptionId=a4cb13896d3, topicName=PD-1/PD-L1)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Fri Feb 19 00:03:33 CST 2021, time=2021-02-19, status=1, ipAttribution=)]
    2021-05-20 liuli5079
  6. [GetPortalCommentsPageByObjectIdResponse(id=1884997, encodeId=4277188499ebf, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Apr 24 18:38:25 CST 2021, time=2021-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1051118, encodeId=fbc1105111870, content=<a href='/topic/show?id=fe74436549' target=_blank style='color:#2F92EE;'>#CD8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4365, encryptionId=fe74436549, topicName=CD8+T)], attachment=null, authenticateStatus=null, 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href='/topic/show?id=4b5c564252' target=_blank style='color:#2F92EE;'>#D8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5642, encryptionId=4b5c564252, topicName=D8+T)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Mon Oct 11 00:38:25 CST 2021, time=2021-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575950, encodeId=09d415e5950f8, content=<a href='/topic/show?id=dc0e6184243' target=_blank style='color:#2F92EE;'>#染色质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61842, encryptionId=dc0e6184243, topicName=染色质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d4ac16256960, createdName=guozhenyu, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605411, encodeId=88981605411e4, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=925371, encodeId=e0339253e198, content=<a href='/topic/show?id=a4cb13896d3' target=_blank style='color:#2F92EE;'>#PD-1/PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=193, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13896, encryptionId=a4cb13896d3, topicName=PD-1/PD-L1)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Fri Feb 19 00:03:33 CST 2021, time=2021-02-19, status=1, ipAttribution=)]
    2021-10-11 gds2009
  7. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605411, encodeId=88981605411e4, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Feb 20 14:38:25 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=925371, encodeId=e0339253e198, content=<a href='/topic/show?id=a4cb13896d3' target=_blank style='color:#2F92EE;'>#PD-1/PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=193, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13896, encryptionId=a4cb13896d3, topicName=PD-1/PD-L1)], attachment=null, 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  8. 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