PURPOSE This study aims to provide comprehensive insights into longitudinal immune landscape in acute myeloid leukemia (AML) development and treatment, which may contribute to predict prognosis and guide clinical decisions. EXPERIMENTAL DESIGN Periphery blood samples from 79 patients with AML (at diagnosis or/and after chemotherapy or at relapse) and 24 healthy controls were prospectively collected. We performed phenotypic and functional analysis of various lymphocytes through multiparametric flow cytometry and investigated prognostic immune-related risk factors. RESULTS Immune defects in AML were reflected in T and natural killer (NK) cells, whereas B-cell function remained unaffected. Both CD8+ T and CD4+ T cells exhibited features of senescence and exhaustion at diagnosis. NK dysfunction was supported by excessive maturation and downregulation of NKG2D and NKP30. Diseased γδ T cells demonstrated a highly activated or even exhausted state through PD-1 upregulation and NKG2D downregulation. Effective therapeutic response following chemotherapy correlated with T and NK function restoration. Refractory and relapsed patients demonstrated even worse immune impairments, and selective immune signatures apparently correlated clinical outcomes and survival. PD-1 expression in CD8+ T cells was independently predictive of poor overall survival and event-free survival. CONCLUSIONS T-cell senescence and exhaustion, together with impaired NK and γδ T-cell function, are dominant aspects involved in immune dysfunction in AML. Noninvasive immune testing of blood samples could be applied to predict therapeutic reactivity, high risk for relapse, and unfavorable prognosis.

中文翻译：

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急性髓细胞性白血病的免疫功能异常特征和与免疫相关的预后因素的鉴定。

目的本研究旨在为急性髓细胞性白血病（AML）的发展和治疗中的纵向免疫格局提供全面的见解，这可能有助于预测预后并指导临床决策。实验设计前瞻性收集了79例AML患者的外周血样本（诊断时，/和/或化疗后或复发时）和24名健康对照。我们通过多参数流式细胞术对各种淋巴细胞进行了表型和功能分析，并调查了与免疫相关的预后危险因素。结果AML的免疫缺陷反映在T细胞和自然杀伤（NK）细胞中，而B细胞功能仍然不受影响。CD8 + T和CD4 + T细胞在诊断时均表现出衰老和衰竭的特征。过高的成熟度和NKG2D和NKP30的下调支持了NK功能障碍。患病的γδT细胞通过PD-1上调和NKG2D下调显示出高度激活或疲惫的状态。化疗后的有效治疗反应与T和NK功能的恢复有关。难治性和复发性患者表现出甚至更严重的免疫损伤，选择性免疫特征显然与临床结局和生存率相关。CD-1 + CD8 + T细胞中的PD-1表达独立预测不良的总生存率和无事件生存率。结论T细胞衰老和衰竭，以及NK和γδT细胞功能受损，是AML免疫功能障碍的主要方面。血液样本的无创免疫测试可用于预测治疗反应性，