文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Liver tumour immune microenvironment subtypes and neutrophil heterogeneity.

作者信息

Xue Ruidong, Zhang Qiming, Cao Qi, Kong Ruirui, Xiang Xiao, Liu Hengkang, Feng Mei, Wang Fangyanni, Cheng Jinghui, Li Zhao, Zhan Qimin, Deng Mi, Zhu Jiye, Zhang Zemin, Zhang Ning

机构信息

Translational Cancer Research Center, Peking University First Hospital, Beijing, China.

BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing, China.

出版信息

Nature. 2022 Dec;612(7938):141-147. doi: 10.1038/s41586-022-05400-x. Epub 2022 Nov 9.


DOI:10.1038/s41586-022-05400-x
PMID:36352227
Abstract

The heterogeneity of the tumour immune microenvironment (TIME), organized by various immune and stromal cells, is a major contributing factor of tumour metastasis, relapse and drug resistance, but how different TIME subtypes are connected to the clinical relevance in liver cancer remains unclear. Here we performed single-cell RNA-sequencing (scRNA-seq) analysis of 189 samples collected from 124 patients and 8 mice with liver cancer. With more than 1 million cells analysed, we stratified patients into five TIME subtypes, including immune activation, immune suppression mediated by myeloid or stromal cells, immune exclusion and immune residence phenotypes. Different TIME subtypes were spatially organized and associated with chemokine networks and genomic features. Notably, tumour-associated neutrophil (TAN) populations enriched in the myeloid-cell-enriched subtype were associated with an unfavourable prognosis. Through in vitro induction of TANs and ex vivo analyses of patient TANs, we showed that CCL4 TANs can recruit macrophages and that PD-L1 TANs can suppress T cell cytotoxicity. Furthermore, scRNA-seq analysis of mouse neutrophil subsets revealed that they are largely conserved with those of humans. In vivo neutrophil depletion in mouse models attenuated tumour progression, confirming the pro-tumour phenotypes of TANs. With this detailed cellular heterogeneity landscape of liver cancer, our study illustrates diverse TIME subtypes, highlights immunosuppressive functions of TANs and sheds light on potential immunotherapies targeting TANs.

摘要

相似文献

[1]
Liver tumour immune microenvironment subtypes and neutrophil heterogeneity.

Nature. 2022-12

[2]
Tumor-Associated Neutrophils Recruit Macrophages and T-Regulatory Cells to Promote Progression of Hepatocellular Carcinoma and Resistance to Sorafenib.

Gastroenterology. 2016-2-26

[3]
Cellular dynamics in tumour microenvironment along with lung cancer progression underscore spatial and evolutionary heterogeneity of neutrophil.

Clin Transl Med. 2023-7

[4]
Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment.

Gut. 2023-5

[5]
Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.

Lung Cancer (Auckl). 2023-11-21

[6]
Harnessing neutrophil plasticity for HCC immunotherapy.

Essays Biochem. 2023-9-28

[7]
Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer.

Br J Cancer. 2020-10

[8]
Tumor-Infiltrating PD-L1+ Neutrophils Induced by GM-CSF Suppress T Cell Function in Laryngeal Squamous Cell Carcinoma and Predict Unfavorable Prognosis.

J Inflamm Res. 2022-2-16

[9]
Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment.

Cancer Biol Med. 2020-2-15

[10]
Neutrophil diversity and plasticity in tumour progression and therapy.

Nat Rev Cancer. 2020-7-21

引用本文的文献

[1]
Preliminary study on SIRI dynamic changes for the efficacy prediction and prognosis evaluation of advanced cancer patients treated with immunotherapy.

Discov Oncol. 2025-9-2

[2]
Spleen granulopoiesis in psoriasis immune microenvironment aggravates psoriasis via IL-6/P-STAT3 signaling.

Biol Direct. 2025-9-2

[3]
Pan-Cancer Integrative Analyses Reveal the Crosstalk Between the Intratumoral Microbiome, TP53 Mutation and Tumour Microenvironment.

IET Syst Biol. 2025

[4]
Spatial Transcriptomics Decodes Breast Cancer Microenvironment Heterogeneity: From Multidimensional Dynamic Profiling to Precision Therapy Blueprint Construction.

Biomolecules. 2025-7-24

[5]
Clonal diversity shapes the tumour microenvironment leading to distinct immunotherapy responses in metastatic urothelial carcinoma.

Nat Commun. 2025-8-27

[6]
Integrating Primary and Metastatic scRNA-Seq and Bulk Data to Develop an Immune-Based Prognosis Signature for Colorectal Cancer.

Curr Issues Mol Biol. 2025-8-13

[7]
Liver-Specific Extracellular Matrix Enables High-Fidelity Patient-Derived Hepatocellular Carcinoma Xenograft Models.

Biomater Res. 2025-8-21

[8]
Single-cell transcriptome analysis identifies MIF as a novel tumor-associated neutrophil marker for pancreatic ductal adenocarcinoma.

NPJ Precis Oncol. 2025-8-20

[9]
A potential strategy to rebuild the tumor immune microenvironment: PANoptosis.

Front Immunol. 2025-8-4

[10]
Target neutrophil heterogeneity and plasticity in cancer.

J Hematol Oncol. 2025-8-12

本文引用的文献

[1]
Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma.

Nat Med. 2022-8

[2]
Neutrophil phenotypes and functions in cancer: A consensus statement.

J Exp Med. 2022-6-6

[3]
CellRank for directed single-cell fate mapping.

Nat Methods. 2022-2

[4]
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

Cell. 2022-1-20

[5]
Comprehensive analysis of spatial architecture in primary liver cancer.

Sci Adv. 2021-12-17

[6]
A single-cell and spatially resolved atlas of human breast cancers.

Nat Genet. 2021-9

[7]
The immunological and metabolic landscape in primary and metastatic liver cancer.

Nat Rev Cancer. 2021-9

[8]
Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion.

Sci Transl Med. 2021-7-28

[9]
Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

J Hepatol. 2021-12

[10]
Conserved pan-cancer microenvironment subtypes predict response to immunotherapy.

Cancer Cell. 2021-6-14

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索