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...

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Autores principales: 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
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Publicado: SAGE Publishing 2021
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spelling oai:doaj.org-article:98cd671eb85e4952aaf95eab47c969342021-11-30T23:35:10ZTumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing2473-974X10.1177/2473974X211059111https://doaj.org/article/98cd671eb85e4952aaf95eab47c969342021-11-01T00:00:00Zhttps://doi.org/10.1177/2473974X211059111https://doaj.org/toc/2473-974XObjective (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.Eric Nisenbaum MDCarly MisztalMikhaylo Szczupak MDTorin ThielhelmStefanie Peña MDChristine Mei MDStefania Goncalves MDOlena BrachoRuixuan Ma MSMichael E. Ivan MDJacques Morcos MDFred Telischi MDXue-Zhong Liu MD, PhDCristina Fernandez-Valle PhDChristine T. Dinh MDSAGE PublishingarticleOtorhinolaryngologyRF1-547SurgeryRD1-811ENOTO Open, Vol 5 (2021)
institution DOAJ
collection DOAJ
language EN
topic Otorhinolaryngology
RF1-547
Surgery
RD1-811
spellingShingle Otorhinolaryngology
RF1-547
Surgery
RD1-811
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
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.
format article
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
title Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing
title_short 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_sort tumor-associated macrophages in vestibular schwannoma and relationship to hearing
publisher SAGE Publishing
publishDate 2021
url https://doaj.org/article/98cd671eb85e4952aaf95eab47c96934
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