Fig. 5: TSP1-mediated immunosuppression and therapeutic implications of targeting glutamatergic excitatory signals.

a Flow cytometry of brain-infiltrating leukocytes (BILs) using a tumor-associated macrophage (TAM)-related marker panel in perampanel (PER)-treated and untreated mice with SB28-TSP1-WT tumors. The data were analyzed and displayed as in Fig. 4c (n = 8 mice per group; p = 0.001; mean: 0.83 [Ctrl] vs. 1.63 [PER]). The box plot shows the median (center line), interquartile range (box limits), and minimum and maximum values (whiskers). b Histogram and bar plot summarizing the suppressive effect of TAMs on CD8+ T-cell proliferation. CD11b+ BILs were isolated from PER-treated and untreated mice with SB28-TSP1-WT tumors (n = 5 mice per group). The data were analyzed as in Fig. 4d. Data are mean ± s.e.m. c Kaplan–Meier survival curves of C57BL/6J mice orthotopically inoculated with SB28-TSP1-WT cells (10,000 cells/1 µL/mouse) and treated with PER (0.75 mg/kg), or vehicle control (Ctrl) via oral gavage, starting the day after tumor inoculation (n = 10 mice per group). d Schematic representation of interactions among glioblastoma cells, neurons, and immune cells, highlighting the key role of TSP1 in crosstalk and summarizing key findings from this study. p values were calculated using the two-sided Welch’s unpaired t-test (a, b) and the Log-rank test c. PC positive control, NC negative control, NS not significant. Source data are provided as a Source Data file. The figure was created in BioRender. Nejo (2025) https://BioRender.com/z1dmf4kd.