Lineage tracking reveals dynamic relationships of T cells in colorectal cancer

生物 CD8型 细胞毒性T细胞 效应器 T细胞受体 T细胞 免疫系统 转录组 细胞生物学 癌症研究 免疫学 遗传学 基因 基因表达 体外
作者
Lei Zhang,Xin Yu,Liangtao Zheng,Yuanyuan Zhang,Yansen Li,Fang Qiao,Ranran Gao,Boxi Kang,Qiming Zhang,Julie Y. Huang,Hiroyasu Konno,Xinyi Guo,Yingjiang Ye,Songyuan Gao,Shan Wang,Xueda Hu,Xianwen Ren,Zhanlong Shen,Wenjun Ouyang
出处
期刊:Nature [Springer Nature]
卷期号:564 (7735): 268-272 被引量:703
标识
DOI:10.1038/s41586-018-0694-x
摘要

T cells are key elements of cancer immunotherapy1 but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8+ effector and ‘exhausted’ T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Treg cell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+ TH1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors —the GZMK+ effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13+BHLHE40+ TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like cells and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers. An integrated RNA-sequencing approach demonstrates that CXCL13+ TH1-like cells are preferentially enriched in microsatellite-instable tumours from patients with colorectal cancer, and IGFLR1 is identified as a co-stimulatory molecule.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
坚强元枫完成签到,获得积分10
刚刚
1秒前
老王家的儿姑娘给老王家的儿姑娘的求助进行了留言
3秒前
酿酿花0729完成签到,获得积分10
3秒前
cici发布了新的文献求助10
3秒前
suhua发布了新的文献求助10
4秒前
6秒前
7秒前
赘婿应助原儿采纳,获得10
8秒前
温暖亦玉完成签到 ,获得积分10
9秒前
9秒前
共享精神应助乔乔兔采纳,获得10
9秒前
漂亮的念双完成签到 ,获得积分10
10秒前
10秒前
个性晓兰完成签到,获得积分10
11秒前
GuGuGaGaAH发布了新的文献求助10
11秒前
科研通AI2S应助一丝禅采纳,获得10
13秒前
zhenenda发布了新的文献求助30
14秒前
suhua完成签到,获得积分20
15秒前
A.y.w完成签到,获得积分10
18秒前
冬吃萝卜夏吃姜完成签到,获得积分10
18秒前
英俊的铭应助GuGuGaGaAH采纳,获得10
20秒前
20秒前
22秒前
zhenenda完成签到,获得积分10
23秒前
愉快的枫叶完成签到 ,获得积分10
25秒前
原儿发布了新的文献求助10
25秒前
热切菩萨发布了新的文献求助150
29秒前
瀛瀛发布了新的文献求助10
30秒前
义气聪展完成签到 ,获得积分10
32秒前
35秒前
35秒前
37秒前
CHOSEN1完成签到,获得积分10
38秒前
微光完成签到,获得积分10
39秒前
AnnChen发布了新的文献求助10
42秒前
12345678发布了新的文献求助10
43秒前
菜鸡完成签到,获得积分10
44秒前
Lucas应助weiv采纳,获得10
44秒前
菜鸡发布了新的文献求助20
47秒前
高分求助中
Heun’s Differential Equations 600
《Fundamentals of Power Supply Design》Robert A. Mammano 510
High Wire: How China Regulates Big Tech and Governs Its Economy 260
lingnan science journal vol. 16 250
The philosophy of sports medicine care: an historical review 250
A posteriori勾配制限手法「ポストリミタ」と界面捕獲法THINCを組み合わせた連続・不連続流れを高解像するMUSCLタイプの解法 210
Thermal behaviours of large scale lithium-ion battery for electric vehicle and hybrid electric vehicle application: a review 200
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2251851
求助须知:如何正确求助?哪些是违规求助? 1900903
关于积分的说明 4744694
捐赠科研通 1690395
什么是DOI,文献DOI怎么找? 856979
版权声明 545578
科研通“疑难数据库(出版商)”最低求助积分说明 453881