Fan Yongfei, Ji Xiang, Yuan Kai, Wu Qiyong, Lou Ming
Department of Thoracic Surgery, The second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213164, People's Republic of China.
Heart and Lung Disease Laboratory, The second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213164, People's Republic of China.
J Inflamm Res. 2025 Mar 8;18:3333-3347. doi: 10.2147/JIR.S509316. eCollection 2025.
Studies have demonstrated that histone deacetylase 1 () enables cancer cells to evade killing mediated by cytotoxic T lymphocytes. However, there are no studies on the immunological aspects of in non-small cell lung cancer (NSCLC).
In this research, we used the Cancer Genome Atlas (TCGA) public database combined with tissue microarray (TMA) to investigate expression and prognosis in NSCLC. According to the median value of expression in the TCGA dataset, samples of patients with NSCLC were classified into high- and low-expression cohorts. Subsequently, the biological characteristics of in high- and low-expression cohorts in terms of signaling pathways, immune cell infiltration, immune cell function, and genomic stability were investigated to better understand the effect of in the tumor microenvironment (TME) of NSCLC. Additionally, we selected tissue samples with overexpression in TMA2 and performed immunohistochemical staining of CD8 T cells to observe the distribution of CD8 T cells in the tumor.
The findings revealed that overexpression of in NSCLC was associated with poor prognosis. Analysis of signaling pathway enrichment indicated that downregulated immune-related signaling pathways in NSCLC. Immune cell infiltration, immune cell function, and genomic stability analyses suggested that the TME alteration mediated by in the high-expression cohort was consistent with the "immune desert" phenotype. Furthermore, CD8 T immunohistochemical staining experiments of tissue samples with overexpression in NSCLC revealed few CD8 T cells distributed in the tumor parenchyma and interstitium.
Conclusively, our findings from several biological analyses revealed that is overexpressed in NSCLC and induces TME immunosuppression.
研究表明,组蛋白去乙酰化酶1()使癌细胞能够逃避细胞毒性T淋巴细胞介导的杀伤作用。然而,关于非小细胞肺癌(NSCLC)中 的免疫学方面尚无研究。
在本研究中,我们使用癌症基因组图谱(TCGA)公共数据库结合组织微阵列(TMA)来研究NSCLC中 的表达和预后。根据TCGA数据集中 表达的中位数,将NSCLC患者的样本分为高表达和低表达队列。随后,研究高表达和低表达队列中 在信号通路、免疫细胞浸润、免疫细胞功能和基因组稳定性方面的生物学特征,以更好地了解 在NSCLC肿瘤微环境(TME)中的作用。此外,我们在TMA2中选择了 过表达的组织样本,并对CD8 T细胞进行免疫组织化学染色,以观察CD8 T细胞在肿瘤中的分布。
研究结果显示,NSCLC中 的过表达与预后不良相关。信号通路富集分析表明, 在NSCLC中下调免疫相关信号通路。免疫细胞浸润、免疫细胞功能和基因组稳定性分析表明,高表达队列中 介导的TME改变与“免疫沙漠”表型一致。此外,NSCLC中 过表达的组织样本的CD8 T免疫组织化学染色实验显示,肿瘤实质和间质中分布的CD8 T细胞很少。
总之,我们从多项生物学分析中得出的结果表明, 在NSCLC中过表达并诱导TME免疫抑制。