Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor‐associated Macrophages

Abstract

ObjectivesThis study compared the immune‐related secretory capacity of human vestibular schwannoma (VS) and tumor‐assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte‐derived macrophages [Mo‐MFs], respectively), and examined relationships with presurgical hearing and tumor size.MethodsVS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+) and TAMs (CD68+) were isolated from VS tissue for culture. The secreted levels of 65 immune‐related factors were measured and compared using unpaired t‐tests with Welch correction (schwannoma vs. SCs) or Mann–Whitney tests (TAMs and Mo‐MFs). Associations between factor concentration and word recognition (WR), pure‐tone average (PTA), and tumor size were evaluated with Spearman correlation.ResultsSecreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL‐2 and BAFF, whereas MMP‐1, IL‐6, FGF‐2, VEGF‐A, MIP‐3α, and GRO‐α concentrations were significantly higher in TAMs versus Mo‐MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin‐3, CD30, and IL‐16 by VS cells; IP‐10, eotaxin‐3, multiple interleukins, GM‐CSF, SCF, and CD30 by TAMs; and TNF‐α and MIP‐1α by Mo‐MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL‐16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL‐7, IL‐21, and LIF by TAMs (all p = 0.017).ConclusionsDifferential secretion of immune‐related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo‐MFs, some of which were correlated with worse hearing and larger VS tumors.Level of EvidenceN/A Laryngoscope, 2023