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

Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Eric Nisenbaum  1 , Carly Misztal  1 , Mikhaylo Szczupak  2 , Torin Thielhelm  1 , Stefanie Peña  1 , Christine Mei  1 , Stefania Goncalves  1 , Olena Bracho  1 , Ruixuan Ma  3 , Michael E Ivan  4 , Jacques Morcos  4 , Fred Telischi  1 , Xue-Zhong Liu  1 , Cristina Fernandez-Valle  5 , Christine T Dinh  1
Affiliations

Tumor-Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Eric Nisenbaum et al. OTO Open. .

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 (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.

Keywords: CD163; CD80; HL; TAM; tumor-associated macrophages; vestibular schwannoma.

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Figures

Figure 1.
Figure 1.
Audiometry and tumor volume. (A, B) Although patients with serviceable hearing had better pure-tone averages and word recognition scores than those with unserviceable hearing, (C) tumor volumes were similar.
Figure 2.
Figure 2.
CD80 and CD163 expression. (A, B) Mean expression levels for CD80 and CD163 were higher in patients with unserviceable hearing vs serviceable hearing. (C) Representative confocal images are shown.
Figure 3.
Figure 3.
Transwell cocultures. Confocal images show monocytes migrated toward vestibular schwannoma (VS) cells associated with serviceable and unserviceable hearing and polarized to M1-type CD80+, M2-type CD163+, or mixed-phenotype macrophages.
Figure 4.
Figure 4.
Direct cocultures. Regardless of hearing status, confocal images demonstrate monocytes polarize predominantly toward M2-type CD163+ macrophages, rather than M1-type CD80+ macrophages, when cultured with vestibular schwannoma (VS) cells.
See this image and copyright information in PMC

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