Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Nisenbaum, Eric; Misztal, Carly; Szczupak, Mikhaylo; Thielhelm, Torin P.; Peña, Stefanie; Mei, Christine; Goncalves, Stefania; Bracho, Olena; Ma, Ruixuan; Ivan, Michael E.; Morcos, Jacques J.; Telischi, Fred F.; Liu, Xuezhong; Fernández‐Valle, Cristina; Dinh, Christine T.

doi:10.1177/2473974x211059111

Cited by 17 publications

(15 citation statements)

References 41 publications

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“…In a meta-analysis by Hannah et al, inflammatory pathways were recognized as likely mediators of vestibular schwannoma hearing loss (22). The discovery of VS specific immune modulatory molecules such as tumor associated macrophages and inflammasomes can be linked to microinflammatory tumor behavior contributing to hearing loss (23,24).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation

Moshtaghi,

Dixon,

Claussen

et al. 2023

Otol Neurotol

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ObjectiveEvaluate for differences in postoperative hearing in patients who undergo immediate versus delayed hearing preservation microsurgical resection of vestibular schwannomas (VS).Study DesignRetrospective single-institution cohort study spanning November 2017 to November 2021.SettingSingle-institution tertiary care hospital.PatientsSporadic VS in patients with American Academy of Otolaryngology–Head and Neck Surgery hearing classification A or B, with tumor size less than or equal to 2 cm and undergoing hearing preservation microsurgical resection.InterventionsDelayed surgical intervention defined by time from first diagnostic MRI to date of surgery being greater than 3 monthsMain Outcome MeasuresPreoperative and postoperative audiometric performance.ResultsIn total, 193 patients met inclusion criteria. Within the cohort, 70 (36%) proceeded with surgery within 3 months of diagnostic MRI with a mean observation time of 62 days, whereas 123 (63%) underwent surgery after 3 months with a mean observation time of 301 days. There was no difference in preoperative hearing between the two groups with word recognition score 99% in early intervention group and 100% in delayed intervention group (p = 0.6). However, 64% of those who proceeded with immediate surgery had successful hearing preservation, compared to a 42% of those who had delayed intervention (p < 0.01). In a multivariable logistic regression accounting for preoperative word recognition score, tumor size, and age at diagnosis, the odds of hearing preservation were lower in those who delayed surgery compared to immediate surgery (odds ratio, 0.31; 95% confidence interval, 0.15–0.61).ConclusionsPatients who underwent microsurgical resection within 3 months of diagnosis demonstrated a hearing preservation advantage compared to those who did not. Findings of this study highlight the counseling challenges associated with the timing of surgical treatment of VS in patients presenting with good preoperative hearing and small tumors.

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Section: Discussionmentioning

confidence: 99%

The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation

Moshtaghi,

Dixon,

Claussen

et al. 2023

Otol Neurotol

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“…Several investigators have demonstrated relationships between inflammatory cytokines, TAMs, and tumor growth in VS (2,6,9,12,28,56); however, the exact roles that M1 and M2 TAMs play in VS are still under debate. In a study performed by De Vries et al (5), the expression of protumorigenic M2 TAMs was linked to tumor growth in sporadic VS.…”

Section: Discussionmentioning

confidence: 99%

“…The exact role that M1 and M2 macrophages have in VS is still under investigation (5)(6)(7). Several investigations have identified associations between cytokines, macrophages, and clinical factors (i.e., hearing loss and tumor progression) in patients with VS (5,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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

Nisenbaum,

Wiefels,

Telischi

et al. 2023

Otol Neurotol

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Background 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. Hypothesis Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. Methods 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. Results 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. Conclusion 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.

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“…The paraffin-embedded tissue blocks were retrieved for retrospective immunohistochemical analysis using a panmacrophage marker (CD68), an M1 marker (CD80), and an M2 marker (CD163). The combination of antibodies against CD80 and CD163 as M1 and M2 markers, respectively, has been previously utilized in multiple immunohistochemistry studies [ 33 , 34 , 35 ]. For quantification, at least four high-power fields (HPFs) were analyzed by a certified pathologist and manually counted in duplicates.…”

Section: Methodsmentioning

confidence: 99%

The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study

Bassiouni

Arens

Zabaneh

et al. 2022

JCM

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The differential involvement of the macrophage activation phenotypes (M1 vs. M2) has been linked to disease severity in various chronic inflammatory disorders. Pharmacologic manipulation of the M1/M2 macrophage polarization has shown therapeutic potential. Cholesteatoma is a destructive chronic middle ear disease with potentially life-threatening complications. The distribution of macrophage polarization phenotypes in middle ear cholesteatoma has not been described. In the present study, human cholesteatoma specimens acquired during tympanomastoidectomy were retrospectively retrieved and immunohistochemically characterized using a combination of antibodies labeling M1 macrophages (CD80), M2 macrophages (CD163), and total macrophages (CD68). The correlations between the immunohistochemical findings and clinical presentation were assessed. The findings revealed that cholesteatomas with more extensive ossicular erosion demonstrated a significantly higher number of M1 (CD80+) cells and a higher M1/M2 ratio than less invasive cholesteatomas (Wilcoxon test, p < 0.05). The extent of ossicular erosion correlated significantly with the M1/M2 ratio (Spearman correlation coefficient ρ = 0.4, p < 0.05). Thus, the degree of ossicular erosion in human acquired cholesteatoma appears to be related to the M1/M2 macrophage polarization. The investigation of macrophage polarization and functions in various clinical presentations of middle ear cholesteatoma is of great interest since it may contribute to the development of pharmaceutical treatment approaches.

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Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Cited by 17 publications

References 41 publications

The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation

The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation

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

The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study

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