TMEM106B in Glioma: Diagnostic Potential and Mechanistic Implications

Backgroup : Gliomas are the most common and aggressive primary brain tumors; their marked heterogeneity and profoundly immunosuppressive microenvironment drive treatment resistance and poor prognosis. TMEM106B, a lysosome-localized transmembrane protein studied in neurodegeneration, has an uncharacterized role in glioma. This study systematically defines TMEM106B expression, clinical significance, and its dual contributions to tumor malignancy and immune microenvironment regulation in glioma. Methods : We employed an integrated, multimodal approach combining clinical specimen analysis, in vitro cellular assays, and in vivo xenograft models to investigate the role of TMEM106B in modulating the glioma immune microenvironment. Results : TMEM106B is markedly overexpressed in glioma tissues and its high expression correlates with worse patient outcomes. Functional enrichment analyses link TMEM106B to immune response–related pathways. TMEM106B expression is significantly negatively correlated with infiltration of key antitumor immune effectors (e.g., natural killer cells and cytotoxic cells), while positively correlated with immune checkpoint molecules (e.g., CD274, PDCD1LG2, TIGIT). In vitro, TMEM106B knockdown markedly suppresses glioma cell proliferation and migration. In vivo, targeting TMEM106B reduces tumor growth in nude mouse xenografts. Conclusion : This study identifies TMEM106B as a novel biomarker and potential therapeutic target in glioma. By concurrently promoting intrinsic malignant phenotypes of tumor cells and shaping an immunosuppressive microenvironment, TMEM106B facilitates glioma progression and provides a rationale for developing combined therapeutic strategies incorporating TMEM106B-targeted approaches and immunotherapy.