Abstract 2745: Tumor microenvironment and host genetics impact glioma progression in a Collaborative Cross-based orthotopic allograft model

Gliomas are diffusely invasive brain tumors with fatal outcomes and few effective treatments. Precision medicine focuses on targeting the genetics of individual tumors, but not host genetics, despite studies that have linked germline polymorphisms with glioma risk. Accordingly, glioma survival studies in mice utilize genetically variable tumors on identical host genetic backgrounds, which fails to differentiate between cancer cell-autonomous (CCA) and tumor microenvironment (TME) effects on glioma progression and host survival. The Collaborative Cross (CC) is a panel of genetically diverse mouse strains derived from both wild- and traditional inbred laboratory strains that facilitates high-resolution genetic mapping in models of complex disease. Here, we implement a novel platform to discover genetic modifiers of both CCA and TME phenotypes using genetically defined orthotopic murine allograft gliomas and CC hosts. We stereotactically injected Nf1;Trp53-/-oligodendrocyte progenitor-derived mouse tumor cells into syngeneic C57BL/6 control mice and 14 different CC strains. Seven strains survived significantly longer than controls (P