Immunogenomic Profiling Reveals a Suppressive Tumor Microenvironment and Immune Evasion Signatures In Glioblastoma
Abstract
Glioblastoma (GBM) is an aggressive brain tumor known for its poor prognosis and resistance to immunotherapy, largely due to a pro-foundly immunosuppressive tumor microenvironment. Understanding the immunogenomic landscape of GBM is critical for identifying biomarkers and therapeutic targets. Transcriptomic data from 45 GBM and 8 normal neural stem cell (NSC) samples were analyzed to iden-tify differentially expressed genes (DEGs). Functional enrichment analysis (GO and KEGG), immune cell infiltration scoring (xCell), and immune checkpoint gene profiling were performed to characterize the tumor immune microenvironment. A total of 15,405 DEGs were iden-tified, including 2,044 upregulated and 13,361 downregulated genes. Notably, AGBL5, FDPS, SLC25A3, NONO, ZDHHC16, and NUTF2 were among the most significantly upregulated genes in GBM. GO and KEGG analyses revealed enrichment of cell cycle and ECM remodeling pathways among upregulated genes, and suppression of immune receptor and cytokine signaling pathways among down-regulated genes. Immune profiling showed increased infiltration of immunosuppressive M2 macrophages and reduced NK and dendritic cell presence in GBM. Furthermore, immune checkpoint genes CD274 (PD-L1), CTLA4, and LAG3 were significantly upregulated, indicating a tumor environment favoring immune evasion. These findings reveal that GBM promotes tumor progression and immune evasion through coordinated gene expression changes and cellular reprogramming of the tumor microenvironment. The identified genes and immune signa-tures represent potential candidates for further investigation as biomarkers and therapeutic targets for overcoming GBM-associated immu-nosuppression.