Abstract
BACKGROUND
Dysregulation of immune checkpoint members within tumors, including glioblastoma (GBM), is related to immune evasion. Herpes virus entry mediator (HVEM) is a novel identified immune checkpoint molecule which plays essential roles in both innate and acquired immunity. Despite recent advances in exploring the function HVEM in a variety cancer types, the clinical and immunological importance of HVEM in human gliomas remain largely unknown.
METHODS
Molecular and clinical data was obtained from publicly genomic databases. Immunohistochemistry was applied to assess the protein level of HVEM. Matlab software as well as R language were used for statistical analysis.
RESULTS
HVEM was found to be elevated in aggressive gliomas, especially in isocitrate dehydrogenase (IDH) wild-type GBM. High expression of HVEM was associated with Mesenchymal subtype and showed promising prognostic values based on Cox regression model and nomogram model. HVEM showed intra-tumor heterogeneity with abundant in peri-necrotic zone and microvascular region. In addition, HVEM high patients were more frequent with genomic aberrations of oncogenic events. Gene ontology and pathway analysis uncovered the enrichment of HVEM in multiple immune regulation process, especially in the suppression of T cell mediated immunity in GBM. Moreover, HVEM was tightly associated with several infiltrating immune and stromal cell lineages in microenvironment, and showed high correlation with other immune checkpoints.
CONCLUSIONS
Our data highlights the importance of HVEM in GBM progression and that targeting HVEM combined with current immune checkpoint blockades might be a novel therapeutic strategy for GBM.
Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection
