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儿童急性白血病免疫微环境的单细胞转录组分析

英文原题:Single-cell transcriptomic analysis of the immune microenvironment in pediatric acute leukemia.

PubMed 2024/06/04(内容时间) Cancer Lett Q1 · IF 11.8(JCR 2025)

研究概要

复发和治疗耐药是儿童B细胞急性淋巴细胞白血病(B-ALL)和急性髓系白血病(AML)管理中面临的重大挑战。

中文摘要

复发和治疗耐药是儿童B细胞急性淋巴细胞白血病(B-ALL)和急性髓系白血病(AML)管理中面临的重大挑战。由于免疫抑制性肿瘤微环境(TME)和缺乏合适的免疫治疗靶点等因素,免疫治疗在白血病中的疗效仍然有限。因此,有必要深入表征儿童白血病的TME以提高免疫治疗的疗效。在此,我们使用单细胞RNA测序(scRNA-seq)来表征儿童B-ALL和AML的TME,特别关注骨髓来源的T细胞。此外,我们研究了儿童AML在起始、缓解和复发阶段的转录组变化。我们的发现揭示了特定的功能表达程序与各种T细胞亚群的波动相关,这可能与AML进展和复发有关。此外,我们对细胞通讯网络的分析确定了VISTA、CD244和TIM3作为儿童AML的潜在免疫治疗靶点。最后,我们在诊断为B-ALL和AML的儿童患者样本中检测到γδ T细胞及相关功能基因比例升高,这可能为开发新的治疗方法提供信息,潜在聚焦于γδ T细胞。

展开英文摘要原文

Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.

论文信息

作者
Yuan J、Zhang J、Zhao B、Liu F、Liu T、Duan Y、Chen Y、Chen X
第一作者单位
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College., Tianjin, China. Electronic address: yuanjiapei@ihcams.ac.cn.China
通讯作者单位
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College., Tianjin, China. Electronic address: zhangyingchi@ihcams.ac.cn.China
文献类型
非美国政府资助研究
期刊
Cancer letters2024 Aug 1
原文标识
PubMed 38844062 · DOI 10.1016/j.canlet.2024.217018