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Liver Cancer:探索可预测肝细胞癌对免疫检查点抑制剂响应的耗竭CD8 T细胞标志物

2021-05-18 yd2015 MedSci原创

CD8-T细胞耗竭可较好的预测肝细胞癌患者ICI治疗的疗效。

逆转CD8-T细胞耗竭是PD1/PDL1为基础的免疫检查点抑制剂(ICI)治疗的主要抗肿瘤机制之一。目前,免疫检查抑制剂也用于晚期肝细胞癌的一线或后线治疗中,比如帕博利珠单抗,纳武利尤单抗、卡瑞利珠单抗等。虽然目前在其他癌种中PDL1、TMB等作为ICI治疗的标志物。但是在肝癌中,这两个指标只有较少一部分。因此,对于肝癌来说仍缺乏较为有效的预测免疫检查点抑制治疗疗效指标。近期,一项发表在Liver Cancer杂志上的研究,探索可预测肝细胞癌对免疫检查点抑制剂应答的耗竭CD8 T细胞的标志物。

研究患者分为两个队列研究,第一个为ICI治疗队列(n=42),又分为试验队列(n=24)和验证队列(n=18);第二个为原发-转移队列。ICI治疗队列的ORR为 37.7%, 没有发现任何临床病理特征跟ORR, PFS或OS有关。ICI治疗队列中,高耗竭CD8-T细胞患者有较好的PFS和OS。

                     耗竭CD8细胞对PFS和OS影响

研究者鉴别出与耗竭CD8-T细胞相关的9基因集(LAG3, CD244, CCL5, CXCL9, CXCL13, MSR1, CSF3R, CYBB, and KLRK1),在ICI治疗应答患者中是高表达的,并且在肿瘤微环境中跟CD8 + LAG3 +细胞的密度有关,同时可独立预测较好的PFS和OS。多因素分析发现9基因集是PFS和OS的独立预后因素。TCGA-LIHC队列也验证9基因集跟PFS或OS有关。

                  不同细胞集对PFS和OS影响

                      鉴别的基因集对PFS和OS影响,TCGA验证

ICI联合治疗和ICI单药治疗在生存以及临床特征等没有明显区别。两组都伴有较高水平的耗竭CD8T细胞浸润。而且9基因集较其他报道的基因集能够更好的预测患者的ORR,PFS和OS。而肝细胞癌肺转移患者中,也发现伴有较高水平的耗竭CD8-T细胞。在转移性肝细胞癌中,也可观察到高水平的调节性T细胞 (CD4 + FoxP3 + 细胞)和我们鉴定的9基因集。

       鉴别基因集在ICI单药和联合组的PFS和OS

综上,CD8-T细胞耗竭可较好的预测肝细胞癌患者ICI治疗的疗效。

原始出处:

Chia-Lang Hsu, Da-Liang Ou, Li-Yuan Bai, et al. Exploring Markers of Exhausted CD8 T Cells to Predict Response to Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma. Liver Cancer. 2021. DOI:10.1159/000515305.

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    2021-11-21 jklm09
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    2021-10-31 hukaixun
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    2021-09-03 xjy02
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  7. [GetPortalCommentsPageByObjectIdResponse(id=1979122, encodeId=938d19e912210, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Jan 09 04:57:21 CST 2022, time=2022-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1852662, encodeId=3f3d1852662ab, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Sun Nov 21 02:57:21 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841682, encodeId=3256184168218, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Sun Oct 31 17:57:21 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863558, encodeId=6f8c1863558b8, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Fri Sep 03 02:57:21 CST 2021, time=2021-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340561, encodeId=45021340561af, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=168, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Thu May 20 04:57:21 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605412, encodeId=28a0160541297, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, 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=Thu May 20 04:57:21 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=966706, encodeId=5f44966e0620, content=话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210518/cd5ae48bc99d4e5b99357ba20b7ae160/700da5bab6de47cba94dcc7b36f23639.jpg, createdBy=f1831296933, createdName=ltxdsr810920, createdTime=Tue May 18 23:36:46 CST 2021, time=2021-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=966600, encodeId=262e9666000f, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue May 18 15:05:43 CST 2021, time=2021-05-18, status=1, ipAttribution=)]
    2021-05-18 ltxdsr810920

    话题

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1979122, encodeId=938d19e912210, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Jan 09 04:57:21 CST 2022, time=2022-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1852662, encodeId=3f3d1852662ab, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Sun Nov 21 02:57:21 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841682, encodeId=3256184168218, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Sun Oct 31 17:57:21 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863558, encodeId=6f8c1863558b8, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Fri Sep 03 02:57:21 CST 2021, time=2021-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340561, encodeId=45021340561af, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=168, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Thu May 20 04:57:21 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605412, encodeId=28a0160541297, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, 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=Thu May 20 04:57:21 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=966706, encodeId=5f44966e0620, content=话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210518/cd5ae48bc99d4e5b99357ba20b7ae160/700da5bab6de47cba94dcc7b36f23639.jpg, createdBy=f1831296933, createdName=ltxdsr810920, createdTime=Tue May 18 23:36:46 CST 2021, time=2021-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=966600, encodeId=262e9666000f, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue May 18 15:05:43 CST 2021, time=2021-05-18, status=1, ipAttribution=)]
    2021-05-18 jyzxjiangqin

    好文章!

    0

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