Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma.

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 2023 Dec 01

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The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80 + M1 and CD163 + M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein ( p = 0.0020), particularly MCP-1 ( p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80 + staining in VS tissue ( r = 0.8852; p = 0.0015) but not CD163 + staining. Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80 + M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention. Copyright © 2023, Otology & Neurotology, Inc.

Citation

Eric Nisenbaum, Matthew Wiefels, Julia Telischi, Mikhail Marasigan, Vivek Kanumuri, Stefanie Pena, Torin Thielhelm, Olena Bracho, Rita Bhatia, Tricia Scaglione, Fred Telischi, Cristina Fernandez-Valle, Xue-Zhong Liu, Evan Luther, Jacques Morcos, Michael Ivan, Christine T Dinh. Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2023 Dec 01;44(10):1073-1081