髓系白血病
肿瘤微环境
细胞毒性T细胞
癌症研究
下调和上调
髓样
骨髓
CD8型
免疫学
白血病
生物
颗粒酶B
颗粒酶
免疫系统
穿孔素
基因
体外
生物化学
作者
Zhiyong Zhang,Cong Deng,Peili Zhu,Danlin Yao,Jianxin Shi,Tiansheng Zeng,Wenhui Huang,Zeyong Huang,Zhihua Wu,Junyi Li,Min Xiao,Lin Fu
出处
期刊:Cancer Science
[Wiley]
日期:2023-08-17
卷期号:114 (10): 3873-3883
被引量:2
摘要
Abstract Acute myeloid leukemia (AML) is a heterogeneous blood cancer. Effective immunotherapies for AML are hindered by a lack of understanding of the tumor microenvironment (TME). Here, we retrieved published single‐cell RNA sequencing data for 128,688 cells derived from 29 bone marrow aspirates, including 21 AML patients and eight healthy donors. We established a global tumor ecosystem including nine main cell types. Myeloid, T, and NK cells were further re‐clustered and annotated. Developmental trajectory analysis indicated that exhausted CD8 + T cells might develop via tissue residual memory T cells (TRM) in the AML TME. Significantly higher expression levels of exhaustion molecules in AML TRM cells suggested that these cells were influenced by the TME and entered an exhausted state. Meanwhile, the upregulation of checkpoint molecules and downregulation of granzyme were also observed in AML NK cells, suggesting an exhaustion state. In conclusion, our comprehensive profiling of T/NK subpopulations provides deeper insights into the AML immunosuppressive ecosystem, which is critical for immunotherapies.
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