Effect of glioblastoma and brain radiotherapy on T-lymphocyte subpopulations in rodents.

Abstract

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⁺-lymphocytes serve as key effectors in cancer immunity. This study aimed to examine the changes in T-lymphocyte subpopulations in both tumor-free and glioblastoma-bearing mice following brain-irradiation. 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⁺-lymphocyte levels. Glioblastoma reduced all T-lymphocyte subpopulations by day 15 post-inoculation. Radiotherapy decreased regulatory and effector CD4⁺-lymphocytes in both tumor-free and glioblastoma-bearing mice, but not naïve or memory CD4⁺-lymphocytes, in both tumor-free and glioblastoma-bearing mice. In tumor-free mice, radiotherapy had no effect on CD8⁺-lymphocytes, but reduced all CD8⁺-lymphocyte types in glioblastoma-bearing mice. Glioblastoma size negatively affected CD8⁺-lymphocytes. Brain-irradiation persistently reduced naïve and memory CD8⁺-lymphocytes, but effector and regulatory T-lymphocytes recovered. Exposure of lymph nodes to radiation worsened CD8⁺-lymphocyte reduction. 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⁺-lymphocytes. Further mechanistic studies are needed to understand the molecular basis of radiation impact on T-lymphocyte subpopulations.