Immune landscape of genetically-engineered murine models of glioma relative to human glioma by single-cell sequencing

Abstract

Glioblastoma (GBM) is the most frequent and deadliest primary brain tumor, with a <10% 5-year overall survival rate. Despite promising results in other disease contexts, deployment of immune system-targeted therapies against GBM has not been successful thus far. In this regard, few preclinical models effectively recapitulate the human GBM immune microenvironment, hindering our ability to identify potentially targetable vulnerabilities. In this study, we characterized tumor immune microenvironment of the Qk/trp53/Pten (QPP) triple-knockout mouse model, harboring alterations common in human GBM and found that tumor infiltrates contain a predominantly myeloid cell population of monocytes, macrophages, and resting dendritic cells, with minor populations of T, B, and NK cells. Notable differences between spontaneous QPP tumors and tumors derived by implanting established QPP cell lines included T-cell enrichment and a larger proportion of myeloid-derived suppressive cells (MDSCs) in implanted tumors. Profiles of myeloid cells subtypes in QPP tumors paralleled findings in human GBMs, suggesting that this model effectively recapitulates the complexity of the myeloid-cell compartment and other human GBM immune cell populations.