最近的研究揭示了组成型 1 型干扰素 (IFN-I) 的产生及其下游信号传导活动在多种恶性肿瘤中的促肿瘤作用。相反，神经胶质瘤中信号传导活性的异质性和临床意义仍然未知。因此，我们的目的是描述神经胶质瘤中组成型 1 型干扰素 (IFN-I) 产生和下游信号传导活性的异质性和临床意义。我们对来自我们队列的 364 个神经胶质瘤组织微阵列使用多重免疫荧光 (mIF)。此外，我们对癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库进行了生物信息分析，以研究胶质瘤中组成型IFN-I信号活性的异质性和临床意义。我们观察到组成型IFN-I的高度异质性。 I 神经胶质瘤亚型之间的信号传导活动。信号随着 WHO 恶性肿瘤等级的增加而增加，而在具有 IDH 突变的神经胶质瘤中则减少。此外，高 IFN-I 活性可作为不良结果的独立预测因子，IDH 突变神经胶质瘤中的整体 DNA 高甲基化与 IFN-I 信号传导活性降低相关。在 IFN-I 活性和神经胶质瘤相关炎症之间观察到正相关，包括抗肿瘤和促肿瘤免疫反应。此外，神经胶质瘤微环境（GME）中肿瘤细胞和免疫细胞的 IFN-I 活性存在显着差异。值得注意的是，在神经胶质瘤亚型之间观察到 GME 细胞中 IFN-I 信号传导活性分布的独特模式，并且该模式与患者总体生存率独立相关。组成性 IFN-I 信号传导活性在神经胶质瘤亚型之间存在显着差异，并且代表了神经胶质瘤亚型增加的潜在指标。神经胶质瘤炎症和不利的临床结果。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下公司）的独家许可。

Recent studies revealed a pro-tumor effect of constitutive Type-1 interferons (IFN-I) production and the downstream signaling activity in several malignancies. In contrast, heterogeneity and clinical significance of the signaling activity in gliomas remain unknown. Thus, we aimed to depict the heterogeneity and clinical significance of constitutive Type-1 interferon (IFN-I) production and the downstream signaling activity in gliomas.We utilized multiplex immunofluorescence (mIF) on a 364 gliomas tissue microarray from our cohort. Moreover, we conducted bioinformatic analyses on the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases to investigate the heterogeneity and clinical significance of constitutive IFN-I signaling activity in gliomas.We observed high heterogeneity of the constitutive IFN-I signaling activity among glioma subtypes. Signaling increased with the WHO malignancy grade while decreasing in the gliomas with IDH mutations. Additionally, high IFN-I activity served as an independent predictor of unfavorable outcomes, and global DNA hypermethylation in IDH-mutant gliomas was associated with decreased IFN-I signaling activity. Positive correlations were observed between the IFN-I activity and glioma-associated inflammation, encompassing both anti-tumor and pro-tumor immune responses. Furthermore, the IFN-I activity varied significantly among tumor and immune cells in the glioma microenvironment (GME). Notably, a distinct pattern of IFN-I signaling activity distribution in GME cells was observed among glioma subtypes, and the pattern was independently associated with patient overall survival.Constitutive IFN-I signaling activity varies significantly among glioma subtypes and represents a potential indicator for increased glioma inflammation and unfavorable clinical outcomes.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.