Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing
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...
Main Authors: | , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Wiley
2021-11-01
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Series: | OTO Open |
Online Access: | https://doi.org/10.1177/2473974X211059111 |
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author | Eric Nisenbaum MD Carly Misztal Mikhaylo Szczupak MD Torin Thielhelm Stefanie Peña MD Christine Mei MD Stefania Goncalves MD Olena Bracho Ruixuan Ma MS Michael E. Ivan MD Jacques Morcos MD Fred Telischi MD Xue-Zhong Liu MD, PhD Cristina Fernandez-Valle PhD Christine T. Dinh MD |
author_facet | Eric Nisenbaum MD Carly Misztal Mikhaylo Szczupak MD Torin Thielhelm Stefanie Peña MD Christine Mei MD Stefania Goncalves MD Olena Bracho Ruixuan Ma MS Michael E. Ivan MD Jacques Morcos MD Fred Telischi MD Xue-Zhong Liu MD, PhD Cristina Fernandez-Valle PhD Christine T. Dinh MD |
author_sort | Eric Nisenbaum MD |
collection | DOAJ |
description | 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 ( P = .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. |
first_indexed | 2024-03-09T08:38:04Z |
format | Article |
id | doaj.art-98cd671eb85e4952aaf95eab47c96934 |
institution | Directory Open Access Journal |
issn | 2473-974X |
language | English |
last_indexed | 2024-03-09T08:38:04Z |
publishDate | 2021-11-01 |
publisher | Wiley |
record_format | Article |
series | OTO Open |
spelling | doaj.art-98cd671eb85e4952aaf95eab47c969342023-12-02T17:49:32ZengWileyOTO Open2473-974X2021-11-01510.1177/2473974X211059111Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to HearingEric Nisenbaum MD0Carly Misztal1Mikhaylo Szczupak MD2Torin Thielhelm3Stefanie Peña MD4Christine Mei MD5Stefania Goncalves MD6Olena Bracho7Ruixuan Ma MS8Michael E. Ivan MD9Jacques Morcos MD10Fred Telischi MD11Xue-Zhong Liu MD, PhD12Cristina Fernandez-Valle PhD13Christine T. Dinh MD14Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Biostatistics, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USABurnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USADepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USAObjective (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 ( P = .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.https://doi.org/10.1177/2473974X211059111 |
spellingShingle | Eric Nisenbaum MD Carly Misztal Mikhaylo Szczupak MD Torin Thielhelm Stefanie Peña MD Christine Mei MD Stefania Goncalves MD Olena Bracho Ruixuan Ma MS Michael E. Ivan MD Jacques Morcos MD Fred Telischi MD Xue-Zhong Liu MD, PhD Cristina Fernandez-Valle PhD Christine T. Dinh MD Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing OTO Open |
title | Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing |
title_full | Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing |
title_fullStr | Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing |
title_full_unstemmed | Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing |
title_short | Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing |
title_sort | tumor associated macrophages in vestibular schwannoma and relationship to hearing |
url | https://doi.org/10.1177/2473974X211059111 |
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