TAMI-28. DIFFERENTIAL MIGRATION MECHANICS AND IMMUNE RESPONSES OF GLIOMA SUBTYPES

Glioblastoma remains a deadly cancer driven by invasion of tumor cells into the brain. Transcriptomic analyses have revealed distinct molecular subtypes, but mechanistic differences that explain clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model for cell migration, 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. 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. ### Competing Interest Statement DAL is the co-founder and co-owner of several biotechnology companies including NeoClone Biotechnologies, Inc., Discovery Genomics, Inc. (recently acquired by immusoft, Inc.), B-MoGen Biotechnologies, Inc. (recently acquired by Bio-Techne Corporation), and Luminary Therapeutics, Inc. DAL holds equity in, serves as a Senior Scientific Advisor for and Board of Director member for Recombinetics, a genome editing company. DAL consults for Genentech, Inc., which is funding some of his research. The business of all these companies is unrelated to the contents of this manuscript.