Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430064, China; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China.
Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113411. doi: 10.1016/j.intimp.2024.113411. Epub 2024 Oct 21.
Immunotherapy is revolutionizing the management of advanced non-small cell lung cancer (NSCLC). However, sustained responses are observed in only a minority of patients. Reliable biomarkers are required to identify potential beneficiaries. Interferon regulatory factor 4 (IRF4) plays a crucial role in immune regulation, suggesting its potential as a prognostic biomarker in NSCLC immunotherapy. This study aimed to investigate the predictive role of IRF4 expression in patients with NSCLC receiving immunotherapy.
Data from three NSCLC cohorts treated with immune checkpoint inhibitors were collected from the Gene Expression Omnibus (GEO) database. The prognostic significance of IRF4 was assessed across these cohorts, and gene set enrichment analysis (GSEA) was performed. IRF4-based nomograms were developed to predict the outcomes of immunotherapy. Correlations among IRF4 expression, immune cell infiltration, and immunotherapy prognosis were evaluated in our cohort.
Elevated IRF4 expression was associated with improved prognosis in patients with NSCLC undergoing immunotherapy, consistent with both GEO dataset and our cohort. IRF4 emerged as an independent predictor for progression-free survival (PFS) and overall survival (OS) in multivariable Cox regression analysis. GSEA analysis highlighted links between IRF4 expression and immune activation pathways such as Chemokine_Signaling_Pathway, Natural_Killer_Cell_Mediated_Cytotoxicity, B_Cell_Receptor_Signaling_Pathway, and T_Cell_Receptor_Signaling_Pathway. In our cohort, immunohistochemistry demonstrated correlations between IRF4 expression and the infiltration of CD8+ T cells, CD20+ B cells, and PD-L1 expression in the tumor microenvironment.
High IRF4 expression in baseline tumor tissue could serve as a favorable predictor of NSCLC immunotherapy outcomes, aiding in personalized treatment strategies.
免疫疗法正在彻底改变晚期非小细胞肺癌（NSCLC）的治疗方式。然而，只有少数患者能获得持续的缓解。需要可靠的生物标志物来识别潜在的获益者。干扰素调节因子 4（IRF4）在免疫调节中起着至关重要的作用，这表明它有可能成为 NSCLC 免疫治疗的预后生物标志物。本研究旨在探讨 IRF4 表达在接受免疫治疗的 NSCLC 患者中的预测作用。
从基因表达综合数据库（GEO）中收集了三个接受免疫检查点抑制剂治疗的 NSCLC 队列的数据。评估了这些队列中 IRF4 的预后意义，并进行了基因集富集分析（GSEA）。开发了基于 IRF4 的列线图来预测免疫治疗的结果。在我们的队列中评估了 IRF4 表达与免疫细胞浸润和免疫治疗预后之间的相关性。
IRF4 表达升高与接受免疫治疗的 NSCLC 患者的预后改善相关，这与 GEO 数据集和我们的队列一致。多变量 Cox 回归分析显示，IRF4 是无进展生存期（PFS）和总生存期（OS）的独立预测因子。GSEA 分析突出了 IRF4 表达与免疫激活途径之间的联系，如趋化因子信号通路、自然杀伤细胞介导的细胞毒性、B 细胞受体信号通路和 T 细胞受体信号通路。在我们的队列中，免疫组织化学显示了 IRF4 表达与肿瘤微环境中 CD8+T 细胞、CD20+B 细胞和 PD-L1 表达浸润之间的相关性。
基线肿瘤组织中高 IRF4 表达可能是 NSCLC 免疫治疗结果的有利预测因子，有助于制定个体化治疗策略。
