Huo Wen, Chen Minxin, Chang Cheng, Yu Jinming, Chen Dawei, Wang Ruozheng
Department of Radiation Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Sci Rep. 2025 Mar 20;15(1):9565. doi: 10.1038/s41598-025-94424-0.
Interferon regulatory factors (IRFs) are integral in governing the expression of Type I interferon (IFN) genes. However, the precise role of IRFs in lung adenocarcinoma remains elusive. Our objective is to elucidate the prognostic implications of IRFs and their potential influence on the immunotherapeutic response in patients with lung adenocarcinoma (LUAD). The association between IRFs expression and clinical as well as prognostic features was evaluated utilizing the TCGA database. Prognostic determinants for LUAD were pinpointed via univariate and multivariate analyses. Nomogram to evaluate prognosis predicated on IRF expression levels. Gene enrichments were conducted to elucidate the mechanisms of action. The degree of immune infiltration was using bioinformatics methods and was validated through a single-cell dataset. We compiled our unique cohort of LUAD patients who underwent anti-PD-1 therapy for subsequent immunohistochemistry and multicolor immunofluorescence staining to gauge the conclusion above. Our findings revealed that IRF8 serves as an independent risk factor for overall survival (OS) in patients with LUAD. An analysis of patients undergoing immunotherapy revealed a positive association between the expression of IRF8 and the response to the treatment. In our specific cohort treated with anti-PD-1, high IRF8 expression was observed to enhance immunotherapy response and prolong OS by modulating immune cell infiltration. Our retrospective analysis suggests that elevated IRF8 expression correlates with improved prognosis in LUAD, with higher IRF8 expression being predictive of a more robust immunotherapy response. Mechanistically, IRF8 expression is associated with a modulated tumor immune microenvironment and improved immunotherapeutic response.
干扰素调节因子（IRFs）在调控I型干扰素（IFN）基因的表达中不可或缺。然而，IRFs在肺腺癌中的具体作用仍不清楚。我们的目标是阐明IRFs对肺腺癌（LUAD）患者的预后影响及其对免疫治疗反应的潜在影响。利用TCGA数据库评估IRFs表达与临床及预后特征之间的关联。通过单因素和多因素分析确定LUAD的预后决定因素。绘制基于IRF表达水平评估预后的列线图。进行基因富集以阐明作用机制。使用生物信息学方法评估免疫浸润程度，并通过单细胞数据集进行验证。我们收集了接受抗PD-1治疗的LUAD患者的独特队列，随后进行免疫组织化学和多色免疫荧光染色以验证上述结论。我们的研究结果表明，IRF8是LUAD患者总生存期（OS）的独立危险因素。对接受免疫治疗的患者进行分析发现，IRF8的表达与治疗反应呈正相关。在我们接受抗PD-1治疗的特定队列中，观察到高IRF8表达通过调节免疫细胞浸润增强免疫治疗反应并延长OS。我们的回顾性分析表明，LUAD中IRF8表达升高与预后改善相关，较高的IRF8表达预示着更强的免疫治疗反应。从机制上讲，IRF8表达与调节肿瘤免疫微环境和改善免疫治疗反应有关。
