A Characterization of the Immune Cells in Immunocompetent and Immunodeficient Mice with Orthotopic Brain Tumors.

BackgroundGlioblastoma is characterized by poor survival with few treatment advances for over 20 years. Active research is being conducted in immunotherapies; however, this may be hampered by the lack of detailed characterization of the immune compartments of orthotopic murine brain tumor models. MethodsWe used cell lines derived from glioblastoma patients and murine glioma cell lines to produce intracranial xenograft and syngraft brain tumors in NSG or C57BL/6 mice, respectively. High-parameter flow cytometry and tissue immunofluorescence staining were used to characterize the immune cell compartment in each model. We investigated brain, spleen, lymph node, and bone marrow for the frequencies of different immune cells. Further, we investigated the effect of sub-lethal whole-body irradiation, commonly used for lymphodepletion, on immune cells in immunocompetent mice. ResultsIn our study of non-tumor-bearing mice, we observed dramatic differences between NSG and C57BL/6 mice, not only of T and B cells but also other immune cells, including decreased monocytes, dendritic cells, and eosinophils. In immunocompetent brain tumor-bearing mice, we observed significant differences in the numbers of immune cells compared to non-tumour-bearing controls, primarily in the brain; however, significant differences were also in the spleen, lymph node and bone marrow, particularly in the subsets of monocytes, T cells and dendritic cells. Sub-lethal irradiation caused lasting changes in immune composition. ConclusionsOur quantitative characterization of different immune compartments in orthotopic murine models of glioblastoma may allow for a better-informed selection of tumor models that are appropriate for the pre-clinical investigation of immunotherapies for glioblastoma.