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对纵向t(8;21)急性髓系白血病的综合单细胞分析揭示了异质性免疫细胞浸润和预后特征。

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

作者信息

Li Xue-Ping, Song Jiang-Tao, Dai Yu-Ting, Zhang Wei-Na, Zhao Bai-Tian, Mao Jia-Ying, Gao Yan, Jiang Lu, Liang Yang

机构信息

Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Front Immunol. 2024 Jul 17;15:1424933. doi: 10.3389/fimmu.2024.1424933. eCollection 2024.

DOI:10.3389/fimmu.2024.1424933
PMID:39086485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11288856/
Abstract

INTRODUCTION

Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis.

METHODS

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.

RESULTS

CD8+ T cells were enriched and and were upregulated in the CD34CD117%-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 and ) 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.

摘要

引言

针对实体癌中T细胞的免疫疗法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）的益处极为有限。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。

方法

通过对原发性和纵向t(8;21) AML样本的多组学研究，我们对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进行了表征。本研究还纳入了更多外部队列。

结果

CD8+ T细胞在CD34CD117%-高组中富集，且 上调；这些特征已知与免疫耗竭有关。单细胞动态数据整合分析显示，一部分T细胞（cluster_2）（高表达 和 ）在复发后的耐药阶段显著进化和扩增。外部队列分析证实，cluster_2 T细胞特征可用于按总生存结果对患者进行分层。

讨论

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

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/1c05d91666c3/fimmu-15-1424933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/cf29b909dfe8/fimmu-15-1424933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/a59005ec836e/fimmu-15-1424933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/0a61e3bd7efb/fimmu-15-1424933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/96026d24f4bb/fimmu-15-1424933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/636dfece61b0/fimmu-15-1424933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/1c05d91666c3/fimmu-15-1424933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/cf29b909dfe8/fimmu-15-1424933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/a59005ec836e/fimmu-15-1424933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/0a61e3bd7efb/fimmu-15-1424933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/96026d24f4bb/fimmu-15-1424933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/636dfece61b0/fimmu-15-1424933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb82/11288856/1c05d91666c3/fimmu-15-1424933-g006.jpg

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