组蛋白去乙酰化酶6（HDAC6）通过诱导上皮-间质转化（EMT）和增强巨噬细胞向M2表型的极化来促进肺腺癌（LUAD）进展。

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

作者信息

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

机构信息

Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Department of Nuclear Medicine, Rizhao People's Hospital, Rizhao, China.

出版信息

NPJ Precis Oncol. 2025 May 22;9(1):150. doi: 10.1038/s41698-025-00949-y.

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.

组蛋白去乙酰化酶6（HDAC6）在肺腺癌（LUAD）的预后及肿瘤免疫微环境（TIME）中起关键作用。本研究利用公共数据集并进行实验验证，发现HDAC6在LUAD中上调，与不良生存结果及以调节性T细胞（Tregs）、癌相关成纤维细胞（CAFs）、M2巨噬细胞和骨髓来源的抑制性细胞（MDSCs）增加为特征的免疫抑制性TIME相关。HDAC6高表达的患者免疫治疗反应降低。HDAC6基因敲除抑制肿瘤生长，抑制PI3K/AKT/mTOR信号传导和上皮-间质转化（EMT），并增强细胞凋亡和M1巨噬细胞募集。HDAC6抑制与抗程序性死亡蛋白1（PD-1）治疗具有协同作用，提示其可能为LUAD治疗的联合策略。HDAC6是LUAD的关键预后标志物和治疗靶点。