Nature:北京大学张泽民研究团队揭示结直肠癌T细胞动态变化

2018-10-30 北大生科院 中国生物技术网

结直肠癌(CRC)是我国常见的消化道恶性肿瘤,但是现今所针对结直肠癌的治疗方案,效果难以令人满意。近年研究报道基因组微卫星不稳定(MSI)/ 错配修复基因缺陷(dMMR)患者对免疫检验点抑制剂PD-1抗体敏感,极大增强了学界从免疫角度治疗CRC的信心。肿瘤浸润T淋巴细胞在肿瘤免疫治疗中发挥核心作用,也是PD-1抗体靶向的主要对象。而我们对肿瘤浸润T淋巴细胞在CRC中的分类和特征仍然缺乏了解,特别对

直肠癌(CRC)是我国常见的消化道恶性肿瘤,但是现今所针对直肠癌的治疗方案,效果难以令人满意。近年研究报道基因组微卫星不稳定(MSI)/ 错配修复基因缺陷(dMMR)患者对免疫检验点抑制剂PD-1抗体敏感,极大增强了学界从免疫角度治疗CRC的信心。肿瘤浸润T淋巴细胞在肿瘤免疫治疗中发挥核心作用,也是PD-1抗体靶向的主要对象。而我们对肿瘤浸润T淋巴细胞在CRC中的分类和特征仍然缺乏了解,特别对于微卫星稳定(MSS)/ 微卫星不稳定(MSI)患者间的T细胞分子差异有待精细的刻画。

2018年10月29日,北京大学张泽民课题组联合美国安进公司(Amgen)欧阳文军团队和北京大学人民医院申占龙课题组在Nature杂志发表了题为“Lineage tracking reveals dynamic relationships of T cells in colorectal cancer”的研究论文,对来自12例结直肠癌初治患者外周血、癌组织及癌旁组织的大量T细胞进行了单细胞全长转录组测序和分析。为了系统性的描述结直肠癌相关T细胞的组织分布特性、克隆性、迁移性和状态转化,研究团队创造性开发了STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking)这一生物信息方法。利用T细胞受体(TCR)作为标签,研究团队发现肿瘤微环境和TCR共同影响了肿瘤浸润CD8 效应记忆T细胞(effector memory T cell)向耗竭性T细胞 (exhausted T cell)和效应T细胞(effector T cell)的转化,这一发现有助于我们理解肿瘤微环境中耗竭性T细胞的来源,并为逆转其状态提供新的思路。

CRC患者中,MSI/dMMR病人对免疫检查点抑制剂的治疗响应显着优于MSS病人。本研究首次从单细胞组学角度对其T细胞差异做出了高精度的比较分析。发现相比MSI病人,TH17细胞富集于MSS病人的肿瘤组织中;而高表达CXCL13的TH1-like细胞(高表达IFNG)在MSI病人中显着富集。这类细胞同时高表达转录因子BHLHE40,它不仅可以促进产生效应性的IFN-?分子,还可以抑制产生抑制性的IL-10分子,提示CXCL13+ TH1-like细胞可能影响到免疫检查点抑制剂的治疗效果。IGFLR1是在CXCL13+ TH1-like的细胞上高表达的一类受体蛋白。本研究通过对IGFLR1及其配体IGFL3的体外实验证明,IGFLR1作为新发现的协同刺激因子,IGFLR1/IGFL3通路可能成为潜在的药物治疗靶点。

最后,研究团队还将CRC T细胞的数据与张泽民课题组之前发表的非小细胞肺癌和肝细胞癌的T细胞数据进行了比较分析。相比于肝癌和肺癌,CRC患者中更多地富集CD160高表达的上皮内淋巴细胞(Intraepithelial lymphocytes)以及TH17细胞,提示了器官区域免疫特征对不同器官肿瘤组织免疫特征的影响,并对解释同一免疫治疗在不同癌种上表现的差异给出了线索。

此项研究是迄今为止国际上对肿瘤微环境中T细胞最为深入新颖的工作。北京大学前沿交叉研究院博士后张雷,美国安进公司炎症与肿瘤部Yu Xin,北京大学前沿交叉研究院博士生郑良涛,生命科学学院博士生张园园为该论文并列第一作者。北京大学生命科学学院BIOPIC中心、北京未来基因诊断高精尖创新中心(ICG)、北大-清华生命科学联合中心张泽民教授,美国安进公司炎症与肿瘤部欧阳文军教授,以及北京大学人民医院肠外科申占龙教授为该论文的共同通讯作者。该研究得到北京未来基因诊断高精尖创新中心(ICG),国家重点研发计划,国家自然科学基金和美国Amgen公司的支持和资助。

原始出处:
Lei Zhang, Xin Yu, Liangtao Zheng, et al.Lineage tracking reveals dynamic relationships of T cells in colorectal cancer.nature.Published: 29 October 2018

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1954386, encodeId=667a195438642, content=<a href='/topic/show?id=f42e330843a' target=_blank style='color:#2F92EE;'>#动态变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33084, encryptionId=f42e330843a, topicName=动态变化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon Feb 11 06:29:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883390, encodeId=e59d1883390ff, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Nov 08 20:29:00 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776370, encodeId=07071e7637000, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Mar 09 22:29:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453177, encodeId=718914531e726, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570051, encodeId=291a15e005179, content=<a href='/topic/show?id=f60de338081' target=_blank style='color:#2F92EE;'>#研究团队#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73380, encryptionId=f60de338081, topicName=研究团队)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=15c315623764, createdName=changhe718, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1954386, encodeId=667a195438642, content=<a href='/topic/show?id=f42e330843a' target=_blank style='color:#2F92EE;'>#动态变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33084, encryptionId=f42e330843a, topicName=动态变化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon Feb 11 06:29:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883390, encodeId=e59d1883390ff, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Nov 08 20:29:00 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776370, encodeId=07071e7637000, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Mar 09 22:29:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453177, encodeId=718914531e726, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570051, encodeId=291a15e005179, content=<a href='/topic/show?id=f60de338081' target=_blank style='color:#2F92EE;'>#研究团队#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73380, encryptionId=f60de338081, topicName=研究团队)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=15c315623764, createdName=changhe718, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=)]
    2018-11-08 liye789132251
  3. [GetPortalCommentsPageByObjectIdResponse(id=1954386, encodeId=667a195438642, content=<a href='/topic/show?id=f42e330843a' target=_blank style='color:#2F92EE;'>#动态变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33084, encryptionId=f42e330843a, topicName=动态变化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon Feb 11 06:29:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883390, encodeId=e59d1883390ff, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Nov 08 20:29:00 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776370, encodeId=07071e7637000, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Mar 09 22:29:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453177, encodeId=718914531e726, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570051, encodeId=291a15e005179, content=<a href='/topic/show?id=f60de338081' target=_blank style='color:#2F92EE;'>#研究团队#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73380, encryptionId=f60de338081, topicName=研究团队)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=15c315623764, createdName=changhe718, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1954386, encodeId=667a195438642, content=<a href='/topic/show?id=f42e330843a' target=_blank style='color:#2F92EE;'>#动态变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33084, encryptionId=f42e330843a, topicName=动态变化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon Feb 11 06:29:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883390, encodeId=e59d1883390ff, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Nov 08 20:29:00 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776370, encodeId=07071e7637000, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Mar 09 22:29:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453177, encodeId=718914531e726, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570051, encodeId=291a15e005179, content=<a href='/topic/show?id=f60de338081' target=_blank style='color:#2F92EE;'>#研究团队#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73380, encryptionId=f60de338081, topicName=研究团队)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=15c315623764, createdName=changhe718, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1954386, encodeId=667a195438642, content=<a href='/topic/show?id=f42e330843a' target=_blank style='color:#2F92EE;'>#动态变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33084, encryptionId=f42e330843a, topicName=动态变化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Mon Feb 11 06:29:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883390, encodeId=e59d1883390ff, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Nov 08 20:29:00 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776370, encodeId=07071e7637000, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Mar 09 22:29:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453177, encodeId=718914531e726, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570051, encodeId=291a15e005179, content=<a href='/topic/show?id=f60de338081' target=_blank style='color:#2F92EE;'>#研究团队#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73380, encryptionId=f60de338081, topicName=研究团队)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=15c315623764, createdName=changhe718, createdTime=Thu Nov 01 06:29:00 CST 2018, time=2018-11-01, status=1, ipAttribution=)]

相关资讯

北京大学健康医疗大数据国家研究院成立

为落实《国务院办公厅关于促进和规范健康医疗大数据应用发展的指导意见》有关要求,助力“健康中国”建设,充分利用北京大学健康医疗大数据相关领域学科齐全、人才聚集、基础雄厚等综合优势,经与国家卫生健康委员会、中国卫生信息与健康医疗大数据学会的长期沟通,研究决定由北京大学与中国卫生信息与健康医疗大数据学会共同建设“北京大学健康医疗大数据国家研究院”。

北京大学成立睡眠医学中心及睡眠协同创新实验室

8月10日,北京大学睡眠研究中心成立,同期还成立了北京大学-宾夕法尼亚大学睡眠协同创新实验室。

打破“围墙” 北京两大医学学科协同发展中心启动

为发挥优势学科的辐射带动作用,提升北京市属医院整体发展水平,引导医院由临床为主向临床科研并重转型,10月23日,北京市医院管理局正式在儿科、消化内科,启动医学学科协同发展中心建设。由北京儿童医院作为牵头单位、首都儿科研究所附属儿童医院作为联合牵头单位的儿科学科协同发展中心,以及由北京友谊医院作为牵头单位的消化内科学科协同发展中心正式授牌。1121842930_15087387037601n.jpg

ELife:北京大学何爱彬研究组等发现PRC2-EED与HDACs控制基因转录抑制程序的新机制

2017年4月10日,国际知名期刊《eLife》杂志在线发表了北京大学分子医学研究所何爱彬研究组和美国哈佛医学院波士顿儿童医院William T. Pu教授共同合作的题为“ EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent”的研究论文。研究回答了组蛋白修饰H3K2

聚焦|勃林格殷格翰与北京大学建立战略伙伴关系,全面合作开展早期科学研究

5月16日 勃林格殷格翰和北京大学宣布了一项雄心勃勃的战略合作计划,旨在共同推动早期科学创新以填补多个治疗领域内未被满足的医疗需求。该战略伙伴合作关系将包含多种合作形式,以便各科研小组以灵活的方式加入该合作。形式包括以具体科研项目为基础的共同研究、博士后奖学金及勃林格殷格翰讲席研究员。该合作旨在加强勃林格殷格翰的早期研究项目管线,帮助勃林格殷格翰站在科技前沿,带来更多具有突破性潜力的、同类第一的新

北京大学睡眠医学中心成立

8月10日,北京大学睡眠研究中心成立,同期还成立了北京大学-宾夕法尼亚大学睡眠协同创新实验室。