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简要通讯:LSD1 抑制增强原发性 AML 细胞对 NK 细胞介导的杀伤的敏感性

英文原题:Brief Communication: LSD1 Inhibition Enhances Susceptibility of Primary AML Cells for NK Cell-Mediated Killing.

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Brief Communication: LSD1 Inhibition Enhances Susceptibility of Primary AML Cells for NK Cell-Mediated Killing.

PubMed 2026/09/14(内容时间) J Immunother Q3 · IF 2.9(JCR 2025)

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中文摘要

急性髓系白血病(AML)是一种预后较差的血液系统恶性肿瘤。近年来,基于自然杀伤(NK)细胞的免疫疗法取得了进展,能够大量扩增NK细胞,并增强其对血液系统恶性肿瘤的细胞毒性。然而,疾病复发仍然是一个挑战。另一个备受关注的治疗干预措施是使用赖氨酸特异性去甲基化酶1(LSD1)抑制剂治疗AML。在此,我们在原代AML样本中研究了LSD1抑制是否能够与体外扩增的NK(exNK)细胞产生协同作用。有趣的是,我们观察到使用LSD1抑制剂bomedemstat和GSK-LSD1处理可导致多种已知能激活NK细胞的应激配体上调。重要的是,这种应激配体表达的增加与NK细胞介导的细胞毒性增强相关,提示这两种疗法具有协同使用的潜力。据我们所知,这是首个评估LSD1抑制与exNK细胞联合应用于AML的研究。

展开英文摘要原文

Acute myeloid leukemia (AML) is a hematological malignancy associated with poor prognosis. Recent developments in natural killer (NK) cell-based immunotherapies have resulted in the robust expansion of NK cells with enhanced cytotoxicity against hematological malignancies.

However, disease relapse remains a challenge. Another therapeutic intervention that has garnered high interest is the use of lysine-specific demethylase 1 (LSD1) inhibitors for AML treatment.

Here, we investigated whether LSD1 inhibition could synergize with ex vivo expanded NK (exNK) cells in a primary AML sample. Interestingly, we observed that treatment with the LSD1 inhibitors, bomedemstat and GSK-LSD1, led to the upregulation of multiple stress ligands known to activate NK cells.

Importantly, this increased stress ligand expression was associated with enhanced NK cell-mediated cytotoxicity, suggesting the potential for both therapies to be used synergistically. To our knowledge, this is the first study to assess the combination of LSD1 inhibition and exNK cells in AML.

论文信息

作者
Sookhaklari M、Moinuddin A、Singh K、Yuksel MT、Mehboob M、Vahedi F、Ashkar AA、Berg T
第一作者单位
Department of Medicine, McMaster University, Hamilton, ON, Canada.Canada
通讯作者单位
Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada.Canada
期刊
Journal of immunotherapy (Hagerstown, Md. : 1997)2026 Sep 14
原文标识
PubMed 42747230 · DOI 10.1097/CJI.0000000000000618