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纵向 t(8;21) AML 的整合单细胞分析揭示异质性免疫细胞浸润和预后特征

英文原题:Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures.

查看英文原题

Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures.

PubMed 2024/07/17(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

我们通过 scRNA-seq 发现了一个与疾病进展和耐药性相关的独特 T 细胞特征。我们的研究提供了一种基于免疫微环境对患者进行分类的新系统。

研究思路结论见上方概要

靶向T细胞的免疫疗法在实体癌中正在彻底改变临床治疗。新型免疫疗法对急性髓系白血病(AML)的获益极为有限。在此,我们对t(8;21) AML患者的免疫微环境进行了表征,以确定免疫细胞浸润状态如何影响预后。

通过对原发性和纵向 t(8;21) AML 样本的多组学研究,我们描述了肿瘤微环境中异质性免疫细胞浸润及其免疫检查点基因表达的特征。本研究还纳入了进一步的外部队列。

在CD34+CD117 dim %-High组中,CD8+ T细胞富集,HAVCR2和TIGIT上调;这些特征已知与免疫耗竭相关。单细胞动态的数据整合分析揭示,T细胞的一个亚群(cluster_2)(高表达GZMB、NKG7、PRF1和GNLY)在复发后的耐药阶段显著演化并扩增。外部队列分析证实,cluster_2 T细胞特征可用于根据总生存期结局对患者进行分层。

展开英文摘要原文

Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research.

CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34 + CD117 dim %-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY ) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome. DISCUSSION: In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.

论文信息

作者
Li XP、Song JT、Dai YT、Zhang WN、Zhao BT、Mao JY、Gao Y、Jiang L
单位
Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.China
期刊
Frontiers in immunology2024
原文标识
PubMed 39086485 · DOI 10.3389/fimmu.2024.1424933