Multiomics analysis of immune correlatives in hepatocellular carcinoma patients treated with tremelimumab plus durvalumab

银耳霉素 杜瓦卢马布 医学 肝细胞癌 免疫学 免疫系统 CD8型 免疫疗法 癌症研究 肿瘤科 无容量 易普利姆玛
作者
Yuta Myojin,Sepideh Babaei,Rajiv Trehan,Caitlin Hoffman,Noémi Kedei,Benjamin Ruf,Mohamed-Reda Benmebarek,Kylynda C. Bauer,Patrick Huang,Chi Ma,Cecilia Monge,Changqing Xie,Donna Mabry Hrones,Austin G. Duffy,Paul Armstrong,Lorenz Kocheise,Fiona Desmond,Jemma Buchalter,Marie Galligan,Colin P. Cantwell
出处
期刊:Gut [BMJ]
卷期号:: gutjnl-334026 被引量:1
标识
DOI:10.1136/gutjnl-2024-334026
摘要

Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC. Objective To study immune responses in HCC patients treated with tremelimumab and durvalumab. Design We treated 28 HCC patients with durvalumab, tremelimumab and locoregional therapies. We performed a high-dimensional multiomics analysis including whole exome sequencing, single-cell RNA seq, CO-Detection by indEXing, flow cytometry and multiplex cytokine/chemokine analysis of patients’ blood and tumour samples and integrated this data to elucidate immune correlatives and response mechanisms. Mice with syngeneic HCC were treated with anti-PD-L1 plus anti-CTLA4 for hepatic lymphocytes, tumour-infiltrating lymphocytes and peripheral blood mononuclear cell analysis. Results The median overall survival was 19.2 months. Tumour tissue analysis revealed enhanced interferon responses, with stronger effects in responders. Gene set variation analysis indicated enhanced antigen presentation in responders. Spatial analysis revealed that non-responder tumours had higher numbers of Tregs located in neighbourhoods enriched with immune cells and expressed higher levels of ICOS and PD-1. Conversely, non-responder PD1+CD8+T in these Treg-enriched neighbourhoods expressed lower ICOS. Cell-communication analysis demonstrated that Treg-CD8+T interaction was enhanced in non-responder tissue. Peripheral blood analysis showed increased classical monocytes in responders and Tregs in non-responders. Treg-CD8+T interaction was confirmed in preclinical models. Finally, single-patient computational analysis from the all-across analysis was performed on 860 features, which led to the identification of multiomics feature sets including Treg features. Conclusion Our study provides a blueprint for in-depth analysis of immune correlates in immunotherapy studies and demonstrates the importance of Treg distribution in HCC. Trial registration numbers NCT02821754 and the EudraCT identifier: 2019-002767-98.
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
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

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
blue发布了新的文献求助10
1秒前
晚灯君完成签到 ,获得积分10
2秒前
UU发布了新的文献求助10
2秒前
lrll完成签到,获得积分10
4秒前
4秒前
lele完成签到,获得积分10
4秒前
hhh发布了新的文献求助10
7秒前
我要看文献完成签到 ,获得积分10
7秒前
wdd完成签到 ,获得积分10
9秒前
李爱国应助开心薯片采纳,获得10
10秒前
11秒前
Z_yiming发布了新的文献求助10
11秒前
爱吃草莓和菠萝的吕可爱完成签到,获得积分10
13秒前
缥缈一刀发布了新的文献求助10
15秒前
小地蛋完成签到 ,获得积分10
16秒前
感谢大哥的帮助完成签到 ,获得积分10
16秒前
614521完成签到,获得积分10
18秒前
111完成签到,获得积分10
19秒前
王先生完成签到 ,获得积分10
19秒前
20秒前
殊荣完成签到,获得积分10
21秒前
JAMA兜里揣完成签到,获得积分10
21秒前
lalala完成签到 ,获得积分10
23秒前
王三歲完成签到,获得积分10
24秒前
你的背包完成签到,获得积分10
24秒前
Yang应助快乐枫采纳,获得10
25秒前
冷傲的如柏完成签到,获得积分10
26秒前
量子星尘发布了新的文献求助10
28秒前
Z_yiming完成签到,获得积分10
28秒前
刘雪晴完成签到 ,获得积分10
28秒前
CCL完成签到,获得积分10
29秒前
缥缈一刀完成签到,获得积分10
30秒前
yar应助坚强幼晴采纳,获得10
30秒前
茶茶完成签到,获得积分0
31秒前
斑点完成签到,获得积分10
31秒前
35秒前
鱼儿乐园完成签到 ,获得积分10
35秒前
XF完成签到,获得积分20
36秒前
36秒前
木之木完成签到,获得积分0
36秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 生物化学 物理 内科学 纳米技术 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 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038303
求助须知:如何正确求助?哪些是违规求助? 3576013
关于积分的说明 11374210
捐赠科研通 3305780
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029