The WYZ-1 mouse glioblastoma stem cell model: A novel preclinical tool for tumor and therapy studies

We established a novel syngeneic glioblastoma stem cell (GSC) line from PDGFB-driven RCAS/tv-a glioblastomas and subsequently generated a Pten-deficient derivative, WYZ-1. In vitro, WYZ-1 cells exhibited robust self-renewal, high expression of GSC markers (CD133, Nestin, SOX2), and multipotent differentiation into neuronal and astrocytic lineages. In vivo, intracranial implantation in immunocompetent mice produced highly infiltrative and vascularized tumors with marked proliferation, necrosis, and white matter invasion, closely recapitulating key histopathological features of human glioblastoma. Immunohistochemical analysis confirmed the retention of oncogenic, stem-like, and mesenchymal-associated markers. Importantly, WYZ-1 tumors displayed an immune-excluded ("cold") tumor microenvironment characterized by dense infiltration of immunosuppressive macrophages/microglial cells within the tumor core and restricted localization of exhausted T cells to the tumor margins. Consistent with these features, WYZ-1 tumors are resistant to temozolomide and anti-PD-1 monotherapy, with only a modest survival benefit observed following CTLA-4 blockade. Collectively, these findings establish WYZ-1 as a highly aggressive, stem-like, and immunocompetent glioblastoma model that mirrors the therapeutic resistance of human disease and provides a valuable platform for investigating tumor biology and evaluating novel immunotherapeutic strategies.