Losartan reprograms the GBM tumor microenvironment. (A) TME-related gene-set enrichment analysis pathways downregulated by losartan treatment compared to control in bulk RNASeq of GL261 tumors (n = 3). (B) Differential gene expression confirms these effects in matrix molecules such as collagen, hypoxia-related genes, and immune checkpoints. Intravital OCT imaging [to detect perfused vessels (red) vs. nonperfused areas (black)] shows that compared to PBS-treated controls (C), losartan (D) renders tumor blood vessels less tortuous and improves tumor perfusion (yellow dashed line—cranial window border; white dashed line—tumor area). (Sequencing: FDR, false discovery rate; all FDR q-values < 0.20; NES, normalized enrichment score; all adjusted P values < 0.05, FC > |2|. Bar plots: mean ± SEM; Student’s unpaired t test; *P < 0.05.)