Invited Talk

Differential Migration Mechanics and Immune Response of Glioblastoma Subtypes

UMN Institute for Engineering in Medicine (IEM), Department of Biomedical Engineering, University of Minnesota, 7-132 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455 USA

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Glioblastoma remains a deadly cancer driven by invasion of tumor cells into the brain. Transcriptomic analyses have revealed distinct molecular subtypes, but mechanistic and targetable differences that explain clinical differences are not clear. Using a state-of-the-art immunocompetent mouse model for glioblastoma – where tumors are induced by injection of plasmids containing human glioblastoma subtype-defining genetic drivers in a wild-type background – we found that, as predicted by the motor-clutch model for cell migration (Klank et al., Cell Rep, 2017), mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their fast migration and comparable proliferation rate in vitro, mice with mesenchymal tumors live longer than mice with proneural tumors, which was correlated with an immune response in the mesenchymal mice that included T cell-mediated killing of cancer cells, similar to human tumors. Thus, mesenchymal tumors have aggressive migration, but are relatively immunologically ‘hot’ which suppresses net proliferation, features which are captured by our Brownian Dynamics tumor simulator (Klank et al., Conv Sci Phys Oncol, 2018). These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies.