Background/Objectives:Interferon alpha (IFNα) remains a cornerstone in the management of Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs), yet its immunomolecular impact over time is not fully elucidated. The aim of the study was to explore how IFNα therapy dynamically reshapes immune and gene profiles in Ph-neg MPNs and assess their potential as treatment-related biomarkers.Methods:This single-center, prospective, observational study included a translational substudy conducted within a previously established clinical cohort of 44 IFNα-treated patients, selecting a representative subset of 18 individuals stratified by treatment duration. Cytokine profiling (ELISA) and gene expression (RT-qPCR) analysis were performed using plasma and peripheral blood mononuclear cells (PBMCs), respectively.Results:Patients with prolonged exposure showed reduced pro-inflammatory cytokines and downregulation of inflammatory-signalling STAT1/STAT3 expression. In contrast, those with intermediate exposure exhibited transient TH2/regulatory cytokine peaks and upregulation of immunomodulatory genes such as CXCL10, SOCS3, and TNFAIP3. Spearman correlations revealed functional associations between cytokine and gene expression patterns including notable links such as STAT1–IL-13 and MYB–IL-13.Conclusions:These results describe a sequential immune reprogramming driven by IFNα, supporting the development of dynamic immunomolecular biomarkers of response in Ph-neg MPNs.
背景/目的：干扰素α（IFNα）仍是费城染色体阴性骨髓增殖性肿瘤（Ph-neg MPNs）治疗的基石，但其长期免疫分子影响尚未完全阐明。本研究旨在探索IFNα治疗如何动态重塑Ph-neg MPNs患者的免疫及基因谱，并评估其作为治疗相关生物标志物的潜力。方法：这项单中心前瞻性观察性研究包含一项转化子研究，基于先前建立的44例IFNα治疗患者临床队列，选取按治疗时长分层的18例代表性患者亚组。分别采用血浆和外周血单个核细胞（PBMCs）进行细胞因子谱分析（ELISA）和基因表达分析（RT-qPCR）。结果：长期暴露患者表现出促炎细胞因子减少及炎症信号通路STAT1/STAT3表达下调。相比之下，中期暴露患者呈现短暂的TH2/调节性细胞因子峰值，以及CXCL10、SOCS3、TNFAIP3等免疫调节基因表达上调。Spearman相关性分析揭示了细胞因子与基因表达模式间的功能关联，包括STAT1–IL-13和MYB–IL-13等显著关联。结论：这些结果描述了IFNα驱动的序贯性免疫重编程过程，为开发Ph-neg MPNs治疗反应的动态免疫分子生物标志物提供了依据。
肿瘤(癌症)患者之家