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前庭神经鞘瘤中的肿瘤相关巨噬细胞及其与听力的关系

Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing.

作者信息

Nisenbaum Eric, Misztal Carly, Szczupak Mikhaylo, Thielhelm Torin, Peña Stefanie, Mei Christine, Goncalves Stefania, Bracho Olena, Ma Ruixuan, Ivan Michael E, Morcos Jacques, Telischi Fred, Liu Xue-Zhong, Fernandez-Valle Cristina, Dinh Christine T

机构信息

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

OTO Open. 2021 Nov 23;5(4):2473974X211059111. doi: 10.1177/2473974X211059111. eCollection 2021 Oct-Dec.

Abstract

OBJECTIVE

(1) Characterize the distribution of M1 and M2 macrophages in vestibular schwannomas by hearing status. (2) Develop assays to assess monocyte migration and macrophage polarization in cocultures with vestibular schwannoma cells.

STUDY DESIGN

Basic and translational science.

SETTING

Tertiary care center.

METHODS

A retrospective chart review of 30 patients with vestibular schwannoma (VS) was performed. Patients were stratified into serviceable and unserviceable hearing groups. Immunohistochemistry for CD80 M1 and CD163 M2 macrophages was conducted. Primary VS cultures (n = 4) were developed and cocultured with monocytes. Immunohistochemistry for macrophage markers was performed to assess monocyte migration and macrophage polarization.

RESULTS

Although tumors associated with unserviceable hearing had higher levels of CD80 and CD163 than those with serviceable hearing, the relationship was only significant with CD163 ( = .0161). However, CD163 level did not remain a significant predictor variable associated with unserviceable hearing on multivariate analysis when adjusted for other variables. In vitro assays show that VS cells induced monocyte migration and polarization toward CD80 M1 or CD163 M2 macrophage phenotypes, with qualitative differences in CD163 macrophage morphologies between serviceable and unserviceable hearing groups.

CONCLUSION

Vestibular schwannomas express varying degrees of CD80 M1 and CD163 M2 macrophages. We present evidence that higher expression of CD163 may contribute to poorer hearing outcomes in patients with VS. We also describe in vitro assays in a proof-of-concept investigation that VS cells can initiate monocyte migration and macrophage polarization. Future investigations are warranted to explore the relationships between tumor, macrophages, secreted cytokines, and hearing outcomes in patients with VS.

摘要

目的

(1)根据听力状况描述M1和M2巨噬细胞在前庭神经鞘瘤中的分布。(2)开发检测方法以评估与前庭神经鞘瘤细胞共培养时单核细胞的迁移和巨噬细胞极化。

研究设计

基础与转化科学。

研究地点

三级医疗中心。

方法

对30例前庭神经鞘瘤(VS)患者进行回顾性病历审查。患者被分为听力尚可和听力丧失两组。进行CD80(M1)和CD163(M2)巨噬细胞的免疫组织化学检测。培养原代VS细胞(n = 4)并与单核细胞共培养。进行巨噬细胞标志物的免疫组织化学检测以评估单核细胞迁移和巨噬细胞极化。

结果

尽管听力丧失相关的肿瘤中CD80和CD163水平高于听力尚可的肿瘤,但仅CD163的这种关系具有统计学意义(P = .0161)。然而,在多变量分析中,当对其他变量进行校正后,CD163水平不再是与听力丧失相关的显著预测变量。体外实验表明,VS细胞可诱导单核细胞迁移并极化至CD80(M1)或CD163(M2)巨噬细胞表型,听力尚可和听力丧失组之间CD163巨噬细胞形态存在质的差异。

结论

前庭神经鞘瘤表达不同程度的CD80(M1)和CD163(M2)巨噬细胞。我们提供的证据表明,CD163的高表达可能导致VS患者听力预后较差。我们还在概念验证研究中描述了体外实验,即VS细胞可引发单核细胞迁移和巨噬细胞极化。未来有必要进行研究以探索VS患者肿瘤、巨噬细胞、分泌的细胞因子与听力预后之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/8638079/0fa30ccd77b8/10.1177_2473974X211059111-fig1.jpg

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