SERPINA3 facilitates malignant progression and remodels tumor immune microenvironment in glioma

Glioblastoma (GBM) have high aggression and immunosuppression characteristics, with treatment limitation and poor clinical prognosis. Glioma-associated macrophages and microglia (GAMs) constitute the majority immune cells in the tumor microenvironment (TME). Differential molecular characteristics in GBM are related to the poor prognosis and result in therapeutic resistance. Previous research revealed that elevated SERPINA3 expression portends a dismal prognosis for glioma patients. However, the relationship between SERPINA3 and glioma malignant progression, as well as its association with GAMs infiltration, remains unclear. In this study, we explored SERPINA3 levels in different grade glioma tissues and its correlation with GAMs markers. We found that an upregulated of SERPINA3 protein expression in GBM tissues compared to low-grade gliomas. Notably, the expressions of CD68 and IBA1, markers for GAMs, were significantly increased in GBM. Furthermore, we observed a strong correlation between high levels of SERPINA3, CD68, and IBA1 with reduced survival in patients with primary gliomas. Intriguingly, within GBM tissues, we further confirmed the expression of SERPINA3 in GAMs, and that SERPINA3 expression is positively associated with CD68 and IBA1 in primary gliomas, indicating remodeling of the tumor immune microenvironment. This study provides an insight into the therapeutic strategy targeting SERPINA3 in glioma patients. • Elevated SERPINA3 is associated with malignant progression and dismal outcomes. • SERPINA3 promotes infiltration of GAMs in glioma, suggesting remodeling of TIME. • In human glioma tissues, SERPINA3 expression is found in GAMs. • This study provides glioma patients with novel strategy targeting SERPINA3.