关键词: immune cells neurofibromatosis type 2 repair cells tumor microenvironment vestibular schwannoma

来  源:   DOI:10.3389/fonc.2024.1340184   PDF(Pubmed)

Abstract:
UNASSIGNED: Vestibular schwannomas (VS), benign tumors stemming from the eighth cranial nerve\'s Schwann cells, are associated with Merlin gene mutations, inflammation, and the tumor microenvironment (TME), influencing tumor initiation, maintenance, and potential neural dysfunction. Understanding TME composition holds promise for systemic therapeutic interventions, particularly for NF2-related schwannomatosis.
UNASSIGNED: A retrospective analysis of paraffin-embedded tissue from 40 patients (2013-2020), evenly divided by neurofibromatosis type 2 status, with further stratification based on magnetic resonance imaging (MRI) progression and hearing function. Immunohistochemistry assessed TME components, including T-cell markers (CD4, CD8, CD25), NK cells (CD7), and macrophages (CD14, CD68, CD163, CCR2). Fiji software facilitated image analysis.
UNASSIGNED: T-cell markers (CD4, CD8, CD7) exhibited low expression in VS, with no significant NF2-associated vs. sporadic distinctions. Macrophage-related markers (CD14, CD68, CD163, CCR2) showed significantly higher expression (CD14: p = 0.0187, CD68: p < 0.0001, CD163: p = 0.0006, CCR2: p < 0.0001). CCR2 and CD163 significantly differed between NF2-associated and sporadic VS. iNOS, an M1-macrophage marker, was downregulated. CD25, a regulatory T-cell marker, correlated significantly with tumor growth dynamics (p = 0.016).
UNASSIGNED: Immune cells, notably monocytes and macrophages, crucially contribute to VS pathogenesis in both NF2-associated and sporadic cases. Significant differences in CCR2 and CD163 expression suggest distinct immune responses. Regulatory T-cells may serve as growth dynamic markers. These findings highlight immune cells as potential biomarkers and therapeutic targets for managing VS.
摘要:
前庭神经鞘瘤(VS),起源于第八脑神经雪旺氏细胞的良性肿瘤,与Merlin基因突变有关,炎症,和肿瘤微环境(TME),影响肿瘤的启动,维护,和潜在的神经功能障碍。了解TME的组成为系统治疗干预提供了希望,特别是NF2相关神经鞘瘤病。
对40例患者(2013-2020年)的石蜡包埋组织的回顾性分析,平均分为神经纤维瘤病2型状态,根据磁共振成像(MRI)进展和听力功能进一步分层。免疫组织化学评估了TME成分,包括T细胞标志物(CD4,CD8,CD25),NK细胞(CD7),和巨噬细胞(CD14、CD68、CD163、CCR2)。斐济软件促进了图像分析。
T细胞标志物(CD4,CD8,CD7)在VS中呈低表达,没有显著的NF2相关vs.零星的区别。巨噬细胞相关标志物(CD14、CD68、CD163、CCR2)显示出显著较高的表达(CD14:p=0.0187,CD68:p<0.0001,CD163:p=0.0006,CCR2:p<0.0001)。NF2相关VS和零星VS之间的CCR2和CD163显着不同。iNOS,M1巨噬细胞标记,被下调。CD25,一种调节性T细胞标志物,与肿瘤生长动力学显著相关(p=0.016)。
免疫细胞,特别是单核细胞和巨噬细胞,在NF2相关和散发性病例中,VS的发病机制至关重要。CCR2和CD163表达的显著差异表明不同的免疫应答。调节性T细胞可用作生长动态标志物。这些发现强调了免疫细胞作为管理VS的潜在生物标志物和治疗靶标。
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