Immune cell regulation in stem cell niche contacting glioblastomas

Bartkowiak T, Lima SM, Hayes MJ, Mistry AM, Sinnaeve J, Leelatian N, Roe CE, Mobley BC, Weaver KD, Thompson RC, Chambless LB, Ihrie RA, Irish JM.
Preprint from
16 February 2022
Glioblastomas (GBM) are tumors for which immune-targeted therapies have failed to show clinical benefit and for which few biomarkers provide context for meaningful therapeutic stratification. Radiographic contact of GBM tumors with the lateral ventricle stem cell niche correlates with worse patient prognosis; however, the extent to which proximity to the ventricle impacts antitumor immunity remains unknown. We demonstrate that T cell checkpoint receptor expression is elevated in ventricle-contacting GBM as is the abundance of a specific, suppressive CD32 + CD44 + HLAD high myeloid population suggesting a distinct immunoregulatory influence on antitumor immunity in proximity to the lateral ventricle. Phospho-specific mass cytometric profiling revealed extensively impaired immune signaling in ventricle-contacting GBM in response to inflammatory cytokine stimulation, further supporting a suppressive milieu influencing immunity at the lateral ventricle. Collectively, we identify a regulatory impact of ventricle contact on antitumor immunity in the brain, and reveal novel clinically targetable mechanisms of immunomodulation in patients with glioblastoma.

Significance Statement

We demonstrate that the immune microenvironment of glioblastoma tumors contacting the lateral ventricle differs from non-contacting tumors. This work connects immune-biology to a radiographically detectable feature, the lateral ventricle, and highlights non-invasive imaging as a means to identify targetable immune features in glioblastoma tumors.