A characterisation of the immune cells in immunocompetent and immunodeficient mice with orthotopic brain tumors.

Objectives: Glioblastoma is characterised by poor survival with few treatment advances for over 20 years. Immunotherapies, which have transformed treatment of other cancers, have been difficult to apply to glioblastoma because of its highly immune-suppressive microenvironment, and there is a growing appreciation that the disease also induces a global suppression of the systemic immune system. However, immunotherapy research is hampered by the lack of detailed characterisation of the whole immune system in murine brain tumor models, with studies until now having focussed mainly on tumor-infiltrating immune cells. Methods: Here, we have studied common murine models of intracranial brain tumors by using high-parameter flow cytometry and tissue immunofluorescence staining to fully characterise immune cells in the brain, draining lymph node, spleen and bone marrow. Results: The highly immune-compromised NSG mouse models were striking in their many immune perturbations, which extended beyond the known deficits in lymphocytes. Immunocompetent tumor models had significant changes in brain-resident immune cells compared to controls, as expected; however, systemic effects were also observed with significant reductions in subsets of monocytes, macrophages and dendritic cells in the spleen and increases in bone marrow. Conclusion: Our extensive and quantitative characterisation of the immune system in murine models of glioblastoma will allow for a better-informed selection of models and advance the search for new immune-based treatments for this deadly disease.