Expressão gênica de biomarcadores de imunossupressão em gliomas de baixo grau e glioblastomas

Abstract

Gliomas, represented by low-grade gliomas (LGG) and glioblastomas (GBM), constitute the most prevalent group of primary malignant tumors of nervous tissue, exhibiting a critical clinical course and poor prognosis. Their biological behavior is associated with the induction of an anti-inflammatory and immunosuppressive state through the modulation of tumor microenvironment components. Immunosuppression allows these tumors to evade immune surveillance and become resistant to immunotherapies. The Programmed Cell Death pathway, represented by the PD-1 and PD-L1 ligands, as well as the adenosinergic axis regulated by the ADO-CD73-A2A triad, play a significant role in the immunomodulatory nature of these tumors. This study investigated the gene expression of the immunosuppressive biomarkers PD-L1 (CD274) and CD73 (NT5E) in LGG and GBM, as well as the correlation between these markers and their potential prognostic value. Tumor samples from patients with LGG (n=17) and GBM (n=19) were analyzed to quantify gene expression levels using RT-qPCR. The results revealed that PD-L1 expression showed no statistically significant difference between LGG and GBM (median values of 0.539 and 1.856, respectively; p=0.922). Similarly, CD73 expression had medians of 0.956 for LGG and 0.252 for GBM, without statistical significance (p=0.070). However, a strong and statistically significant positive correlation was observed between PD-L1 and CD73 in GBM (r=0.714; p=0.003), while in LGG the correlation was not significant (p=0.255). These findings suggest that, in GBM, the immunosuppressive pathways mediated by PD-L1 and CD73 may act interdependently, indicating a more immunosuppressive tumor microenvironment. The co-expression of these biomarkers in GBM may have implications for the development of combined therapeutic strategies targeting multiple immune checkpoints to optimize treatment response.