Molecular Characterization and Immune Modulation of Schwann Cells in Vestibular Schwannoma

Abstract

Vestibular schwannoma (VS) is a benign tumor originating from the vestibular nerve, and its complex tumor microenvironment presents significant challenges for research. This study employs single-cell transcriptome sequencing to comprehensively investigate the molecular characteristics of Schwann cells within VS and their potential immunoregulatory roles in the tumor microenvironment. We identified a novel subpopulation of Schwann cells, termed Schwann 4, which shows significantly expressed MHC class II molecules and co-enrichment of PI3K signaling, focal adhesion, and cell adhesion-related pathways, suggesting its potential involvement in tumor-immune modulation. Utilizing machine learning models, we pinpointed 179 genes significantly expressed in Schwann 4, with CTSZ emerging as a candidate gene. CTSZ expression is elevated in VS and is significantly correlated with the PI3K pathway. Comparative analysis revealed that CTSZ promotes proliferation in malignant CNS tumors, whereas its role in benign VS appears distinct. Experimental analysis revealed that CTSZ is correlated with regulatory T cells (Tregs) functionality markers via the PVR-TIGIT pathway, suggesting a potential mechanism for Schwann cell-mediated immune modulation. Functional assays further demonstrated that CTSZ knockdown impairs cell migration and focal adhesion kinase activity. Drug sensitivity analyses identified candidate agents such as YM201636 and AT7867, though their applicability to VS requires dedicated validation. This study contributes to understanding the molecular mechanisms of Schwann cells in benign nerve sheath tumors while providing preliminary evidence for future therapeutic investigation.