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人前庭神经鞘瘤细胞和肿瘤相关巨噬细胞分泌因子的免疫谱分析。

Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor-associated Macrophages.

机构信息

Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, U.S.A.

Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, U.S.A.

出版信息

Laryngoscope. 2024 Mar;134 Suppl 5:S1-S14. doi: 10.1002/lary.31067. Epub 2023 Sep 30.

Abstract

OBJECTIVES

This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size.

METHODS

VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B ) and TAMs (CD68 ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation.

RESULTS

Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017).

CONCLUSIONS

Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors.

LEVEL OF EVIDENCE

N/A Laryngoscope, 134:S1-S14, 2024.

摘要

目的

本研究比较了人前庭神经鞘瘤(VS)与肿瘤辅助巨噬细胞(TAMs)的免疫相关分泌能力与其正常对应物(雪旺细胞[SCs]和外周血单核细胞衍生的巨噬细胞[Mo-MFs]),并研究了其与术前听力和肿瘤大小的关系。

方法

使用 16 例 VS 肿瘤、1 例听神经、9 例血液和 3 例耳大神经。从 VS 组织中分离 SCs(S100B)和 TAMs(CD68)进行培养。使用未配对 t 检验(schwannoma vs. SCs)或 Mann-Whitney 检验(TAMs 和 Mo-MFs)比较 65 种免疫相关因子的分泌水平。使用 Spearman 相关性评估因子浓度与言语识别(WR)、纯音平均听阈(PTA)和肿瘤大小之间的关系。

结果

与 SCs 上清液相比,雪旺细胞瘤中分泌浓度明显更高的因子包括 IL-2 和 BAFF,而 MMP-1、IL-6、FGF-2、VEGF-A、MIP-3α 和 GRO-α在 TAMs 中的浓度明显高于 Mo-MFs(均 p < 0.05)。WR 越差与 VS 细胞分泌的 fractalkine、eotaxin-3、CD30 和 IL-16 显著相关;TAMs 分泌的 IP-10、eotaxin-3、多种白细胞介素、GM-CSF、SCF 和 CD30;Mo-MFs 分泌的 TNF-α和 MIP-1α(均 p < 0.05)。PTA 越差与 VS 细胞分泌的 IL-16 显著相关(p < 0.05)。肿瘤越大与 VS 细胞分泌的 eotaxin 以及 TAMs 分泌的 IL-7、IL-21 和 LIF 显著相关(均 p = 0.017)。

结论

在雪旺细胞瘤与正常 SCs 之间以及 TAMs 与 Mo-MFs 之间观察到免疫相关因子的差异分泌,其中一些与听力下降和 VS 肿瘤增大有关。

证据水平

无。喉镜,134:S1-S14,2024。

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