Integrative analysis identified the key role of LAG3 in T cell exhaustion in glioma

Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint expressed on the surface of T cells. We conducted a comprehensive molecular characterization and clinical analysis of LAG3 expression in gliomas. Across the CGGA and TCGA glioma datasets, we observed that LAG3 expression increased with higher glioma grade. Further investigation into the molecular subtypes revealed that LAG3 exhibited the highest expression in the Mesenchymal subtype, similar to other immune checkpoints. CIBERSORT analysis showed a significant positive correlation between LAG3 expression and macrophages, suggesting LAG3's involvement in shaping the immune microenvironment. Single-cell data indicated that LAG3 expression appeared to be exclusive to other immune checkpoints, implying multiple mechanisms of T cell exhaustion. Importantly, clinical data analysis demonstrated that elevated LAG3 expression is an independent poor prognostic factor for patient survival. These findings suggest that LAG3 may play a crucial role in regulating the immune microenvironment in gliomas and contribute to T cell exhaustion, alongside other immune checkpoints such as the PD-L1/PD-1 pathway. As such, LAG3 represents a potential therapeutic target for glioma immunotherapy.