PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-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.
UNASSIGNED: 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：
■在实体癌中靶向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细胞性白血病（AML）的益处极为有限。这里,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，我们表征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。进一步的外部队列也包括在这项研究中。
■在CD34+CD117dim%-High组中CD8+T细胞富集并且HAVCR2和TIGIT上调;已知这些特征与免疫耗竭相关。单细胞动力学的数据整合分析显示，T细胞亚群（簇_2）（高表达GZMB，NKG7，PRF1和GNLY）在复发后的耐药阶段发生了明显的演变和扩展。外部队列分析证实，簇_2T细胞特征可用于根据总体生存结果对患者进行分层。
■总而言之，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。
■通过对原发性和纵向t(8;21)AML样本的多组学研究，我们表征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。进一步的外部队列也包括在这项研究中。
■在CD34+CD117dim%-High组中CD8+T细胞富集并且HAVCR2和TIGIT上调;已知这些特征与免疫耗竭相关。单细胞动力学的数据整合分析显示，T细胞亚群（簇_2）（高表达GZMB，NKG7，PRF1和GNLY）在复发后的耐药阶段发生了明显的演变和扩展。外部队列分析证实，簇_2T细胞特征可用于根据总体生存结果对患者进行分层。
■总而言之，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。
