HDAC6通过诱导EMT和增强巨噬细胞向M2表型的极化来促进LUAD的进展。

IF 6.8 1区医学 Q1 ONCOLOGY

NPJ Precision Oncology Pub Date : 2025-05-22 DOI:10.1038/s41698-025-00949-y

Yantao Jiang, Ju Zhang, Junjie Yu, Wei Luo, Qingwu Du, Wenting Liu, Qi Xu, Xueyang Li, Huiyan Liu, Dingzhi Huang, Tingting Qin

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引用次数: 0

摘要

组蛋白去乙酰化酶6 （HDAC6）在肺腺癌（LUAD）预后和肿瘤免疫微环境（TIME）中起关键作用。这项利用公开数据集和实验验证的研究显示，HDAC6在LUAD中上调，与较差的生存结果和以Tregs、CAFs、M2巨噬细胞和MDSCs增加为特征的免疫抑制时间相关。hdac6高的患者免疫治疗反应降低。敲除HDAC6抑制肿瘤生长，抑制PI3K/AKT/mTOR信号和EMT，增强细胞凋亡和M1巨噬细胞募集。HDAC6抑制与抗pd -1治疗协同作用，提示LUAD治疗的潜在组合策略。HDAC6是LUAD的关键预后指标和治疗靶点。

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HDAC6 facilitates LUAD progression by inducing EMT and enhancing macrophage polarization towards the M2 phenotype.

Histone deacetylase 6 (HDAC6) plays a critical role in lung adenocarcinoma (LUAD) prognosis and the tumor immune microenvironment (TIME). This study, utilizing public datasets and experimental validation, revealed that HDAC6 is upregulated in LUAD, correlating with poor survival outcomes and an immunosuppressive TIME characterized by increased Tregs, CAFs, M2 macrophages, and MDSCs. HDAC6-high patients showed reduced immunotherapy response. HDAC6 knockout inhibited tumor growth, suppressed PI3K/AKT/mTOR signaling and EMT, and enhanced apoptosis and M1 macrophage recruitment. HDAC6 inhibition synergized with anti-PD-1 therapy, suggesting a potential combinatorial strategy for LUAD treatment. HDAC6 serves as a key prognostic marker and therapeutic target in LUAD.

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来源期刊

NPJ Precision Oncology ONCOLOGY-

CiteScore

9.90

自引率

1.30%

发文量

审稿时长

18 weeks

期刊介绍： Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.