急性髓系白血病（AML）是一种异质性的血液癌症。AML的有效免疫疗法受到肿瘤微环境（TME）缺乏理解的限制。本文中，我们检索了包括21例AML患者和8例健康供体在内的29个骨髓抽吸物中获得的共128,688个细胞的已发表的单细胞RNA测序数据。我们建立了一个包含九个主要细胞类型的全局肿瘤生态系统。髓系细胞，T细胞和NK细胞进一步进行了重新聚类和注释。发育轨迹分析表明，疲劳CD8+T细胞可能通过组织残留记忆T细胞（TRM）在AML TME中发展。AML TRM细胞中显著高的疲劳分子表达水平表明这些细胞受到了TME的影响并进入了疲劳状态。同时，在AML NK细胞中观察到了检查点分子的上调和粒酶的下调，表明这些细胞也处于疲劳状态。总之，我们对T/NK亚群的全面描述提供了更深入的洞察AML免疫抑制生态系统，这对于免疫疗法至关重要。© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.