← 返回前沿论文

前庭神经鞘瘤肿瘤微环境组成分析:对 NF2 相关性和散发性变异及其临床相关性的见解

英文原题:Analysis of tumor microenvironment composition in vestibular schwannomas: insights into NF2-associated and sporadic variations and their clinical correlations.

PubMed 2024/05/16(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

研究概要

免疫细胞,尤其是单核细胞和巨噬细胞,在NF2相关和散发性病例的VS发病机制中均起关键作用。CCR2和CD163表达的显著差异提示存在不同的免疫反应。调节性T细胞可能作为生长动态标志物。这些发现凸显了免疫细胞作为管理VS的潜在生物标志物和治疗靶点。

研究思路结论见上方概要

前庭神经鞘瘤(VS)是起源于第八脑神经施万细胞的良性肿瘤,与Merlin基因突变、炎症及肿瘤微环境(TME)相关,影响肿瘤的发生、维持及潜在的神经功能障碍。了解TME的组成有望为系统性治疗干预带来希望,尤其是针对NF2相关神经鞘瘤病。

对40例患者(2013-2020年)的石蜡包埋组织进行回顾性分析,按2型神经纤维瘤病状态平均分组,并根据磁共振成像(MRI)进展和听力功能进一步分层。免疫组化评估了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)。使用Fiji软件进行图像分析。

T细胞标志物(CD4、CD8、CD7)在VS中呈低表达,NF2相关性与散发性之间无显著差异。巨噬细胞相关标志物(CD14、CD68、CD163、CCR2)表达显著升高(CD14:p = 0.0187,CD68:p < 0.0001,CD163:p = 0.0006,CCR2:p < 0.0001)。CCR2和CD163在NF2相关性与散发性VS之间差异显著。iNOS作为一种M1型巨噬细胞标志物,呈下调表达。CD25作为一种调节性T细胞标志物,与肿瘤生长动力学显著相关(p = 0.016)。

展开英文摘要原文

OBJECTIVE: 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. METHODOLOGY: 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. RESULTS: 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). DISCUSSION: 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.

论文信息

作者
Nickl V、Ziebolz D、Rumpel C、Klein D、Nickl R、Rampeltshammer E、Monoranu CM、Ernestus RI
单位
Department of Neurosurgery, Section Experimental Neurosurgery, University Hospital W&#xfc;rzburg, W&#xfc;rzburg, Germany.Germany
期刊
Frontiers in oncology2024
原文标识
PubMed 38817895 · DOI 10.3389/fonc.2024.1340184