The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma

肝细胞癌 流式细胞术 转录组 细胞因子 癌症研究 生物 免疫学 先天性淋巴细胞 免疫系统 先天免疫系统 基因表达 基因 生物化学
作者
Bernd Heinrich,E. Michael Gertz,Alejandro A. Schäffer,Amanda J. Craig,Benjamin Ruf,Varun Subramanyam,John C. McVey,Laurence P. Diggs,S. Heinrich,Umberto Rosato,Chi Ma,Chunhua Yan,Ying Hu,Yongmei Zhao,Tsai-Wei Shen,Veena Kapoor,William G. Telford,David E. Kleiner,Merril K Stovroff,Harmeet Dhani,Ji‐Man Kang,Thomas Fishbein,Xin Wei Wang,Eytan Ruppin,Alexander Kroemer,Tim F. Greten,Firouzeh Korangy
出处
期刊:Gut [BMJ]
卷期号:71 (6): 1161-1175 被引量:72
标识
DOI:10.1136/gutjnl-2021-325288
摘要

Objective Hepatocellular carcinoma (HCC) represents a typical inflammation-associated cancer. Tissue resident innate lymphoid cells (ILCs) have been suggested to control tumour surveillance. Here, we studied how the local cytokine milieu controls ILCs in HCC. Design We performed bulk RNA sequencing of HCC tissue as well as flow cytometry and single-cell RNA sequencing of enriched ILCs from non-tumour liver, margin and tumour core derived from 48 patients with HCC. Simultaneous measurement of protein and RNA expression at the single-cell level (AbSeq) identified precise signatures of ILC subgroups. In vitro culturing of ILCs was used to validate findings from in silico analysis. Analysis of RNA-sequencing data from large HCC cohorts allowed stratification and survival analysis based on transcriptomic signatures. Results RNA sequencing of tumour, non-tumour and margin identified tumour-dependent gradients, which were associated with poor survival and control of ILC plasticity. Single-cell RNA sequencing and flow cytometry of ILCs from HCC livers identified natural killer (NK)-like cells in the non-tumour tissue, losing their cytotoxic profile as they transitioned into tumour ILC1 and NK-like-ILC3 cells. Tumour ILC composition was mediated by cytokine gradients that directed ILC plasticity towards activated tumour ILC2s. This was liver-specific and not seen in ILCs from peripheral blood mononuclear cells. Patients with high ILC2/ILC1 ratio expressed interleukin-33 in the tumour that promoted ILC2 generation, which was associated with better survival. Conclusion Our results suggest that the tumour cytokine milieu controls ILC composition and HCC outcome. Specific changes of cytokines modify ILC composition in the tumour by inducing plasticity and alter ILC function.
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
mhuim发布了新的文献求助10
8秒前
可靠的亦竹完成签到 ,获得积分10
11秒前
11秒前
mhuim完成签到,获得积分20
16秒前
猪猪hero发布了新的文献求助10
17秒前
18秒前
19秒前
折柳完成签到 ,获得积分10
20秒前
一只鱼完成签到,获得积分10
20秒前
23秒前
落后月亮发布了新的文献求助10
24秒前
mad完成签到 ,获得积分10
26秒前
28秒前
要减肥听南完成签到,获得积分10
28秒前
心静听炊烟完成签到,获得积分10
29秒前
卿莞尔完成签到 ,获得积分10
30秒前
自由梦露完成签到,获得积分10
30秒前
31秒前
xinghun910发布了新的文献求助10
31秒前
huohuo143完成签到,获得积分10
32秒前
hhhhhhl完成签到,获得积分10
34秒前
落后月亮完成签到,获得积分10
36秒前
飘逸秋荷完成签到,获得积分10
37秒前
38秒前
李爱国应助自由梦露采纳,获得10
38秒前
娜娜完成签到,获得积分10
39秒前
bc应助宇辰采纳,获得30
40秒前
忧心的惜天完成签到 ,获得积分10
40秒前
MBL发布了新的文献求助10
41秒前
bkagyin应助77采纳,获得10
41秒前
kinase完成签到 ,获得积分10
43秒前
星辰大海应助忧心的惜天采纳,获得10
44秒前
44秒前
dique3hao完成签到 ,获得积分10
45秒前
47秒前
香蕉觅云应助lynn采纳,获得10
48秒前
重要的冰绿完成签到,获得积分10
52秒前
栖迟发布了新的文献求助10
54秒前
serena完成签到,获得积分10
54秒前
54秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
ISCN 2024 – An International System for Human Cytogenomic Nomenclature (2024) 3000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
Mindfulness and Character Strengths: A Practitioner's Guide to MBSP 380
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3776256
求助须知:如何正确求助?哪些是违规求助? 3321728
关于积分的说明 10207386
捐赠科研通 3036979
什么是DOI,文献DOI怎么找? 1666508
邀请新用户注册赠送积分活动 797517
科研通“疑难数据库(出版商)”最低求助积分说明 757868