Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types (see companion study SDY1658)

Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. We generated distinct imageable syngeneic mouse GBM-tumor models and utilized RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells, resident macrophages and fewer eosinophils and SiglecF+ macrophages. To mimic the clinical settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decrease in resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM-tumors showed stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.