Immunosuppressive MDSC and Treg signatures predict prognosis and therapeutic response in glioma.

ABSTRACT

Glioma, a complex and aggressive brain tumor, is characterized by dysregulated immune responses within the tumor microenvironment (TME). We conducted a comprehensive analysis to elucidate the roles of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in glioma progression and their impact on the immune landscape. Using transcriptome data, we stratified glioma samples based on MDSC and Treg levels, revealing significant differences in patient survival probabilities. LASSO regression identified a gene panel associated with glioma prognosis, yielding a patient-specific risk score. Multivariate Cox regression confirmed the risk score's correlation with overall survival. An ISS (immune suppressive score) system assessed the immune landscape's impact on glioma progression and therapeutic response. Functional validation showed MDSC and Treg infiltration's relevance in glioma progression and immune modulation. Hub genes in the black module, including CCL2, LINC01503, CXCL8, CLEC2B, TIMP1, and RGS2, were identified through MCODE analysis. RGS2 expression correlated with immune cell populations and varied in glioma cells. This study sheds light on MDSCs' and Tregs' roles in glioma pathogenesis, suggesting their potential as prognostic biomarkers and therapeutic targets for personalized immunotherapeutic strategies in glioma treatment.