INTRODUCTION: Although lymphopenia is linked to immune suppression favoring tumor growth, the effect of different radiation types on specific T-lymphocyte subsets remains unclear. Among the T-lymphocyte subpopulations, CD8 METHODS: The study was divided into two main phases. First, C57BL/6 mice, with or without glioblastoma (GL261 cells), received hemispheric brain-irradiation or no-treatment. T-lymphocyte subpopulations were analyzed using flow cytometry at various timepoint. The effect of tumor size and brain-irradiation on these cells was assessed using correlation analysis. Next, C57BL/6 mice were subjected to different brain-irradiation conditions. Blood samples were collected during and post-irradiation to analyze T-lymphocyte subpopulations, and tree-based modeling was used to determine radiation parameters impact on naïve CD8 RESULTS: Glioblastoma reduced all T-lymphocyte subpopulations by day 15 post-inoculation. Radiotherapy decreased regulatory and effector CD4 CONCLUSION: These findings confirm that the presence of glioblastoma and brain-irradiation affect T-lymphocyte subpopulations in mice. The inclusion of lymph nodes in the irradiated area led to a long-term decrease in naïve CD8