Roles of Tenascin-XB in the Glioma Immune Microenvironment

Background: Previous studies have reported the critical roles of tumor cells and the tumor microenvironment in tumor prognosis and immunotherapeutic response. However, how Tenascin-XB (TNXB) expression relates to glioma prognosis and to the levels of tumor-infiltrating immune cells in various cancers has remained elusive. Therefore, this work aimed to investigate the expression, prognostic value, biological function and correlation between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues.Methods: First, we explored TNXB expression in glioma tissues by using online biological databases. Second, we assessed the clinical importance of TNXB expression with chi-squared tests, Cox regression and Kaplan-Meier curve analyses. Third, we examined the relationship between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues in an online database. Additionally, we assessed the associations of TNXB expression with genetic markers of immune cells and common immune-checkpoint molecules.Results: Elevated TNXB expression in glioma tissues correlated with tumor grade, according to several databases. Elevated TNXB expression was significantly associated with negative clinicopathological manifestations and poorer prognosis, on the basis of TCGA (n=510) data. Furthermore, univariate and multivariate Cox regression indicated that TNXB was an independent indicator of glioma prognosis. Pathway enrichment analyses suggested that TNXB participates in the immune response, humoral immune response and interferon-gamma-mediated signaling pathways. Importantly, TNXB expression was significantly associated with higher levels of tumor-infiltrating immune cells in diverse cancers. Furthermore, TNXB expression was strongly associated with genetic markers of immune cells and common immune-checkpoint molecules (e.g., PD-1, PD-L1, CTLA4, TIM-3, LAG3, PDCD1LG2, TIGIT and Siglec-15).Conclusions: TNXB expression correlates with poorer prognosis and higher levels of tumor-infiltrating immune cells in several cancers. In addition, TNXB expression is likely to contribute to the regulation of dendritic cells, exhausted T cells, regulatory T cells and tumor-associated macrophages in gliomas. Consequently, TNXB may serve as an important prognostic marker and may play an immunomodulatory role in tumors.