Abstract
Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.