TMIC-51. SEX-SPECIFIC T CELL BEHAVIOR DRIVES DIFFERENTIAL IMMUNE RESPONSES IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor and shows poor outcomes as a median survival 12-18 months with current standard-of-care of therapy. GBM exhibits sex differences in incidence overall survival, males experiencing higher worse prognosis compared to females. However, role immune cells outside myeloid remains poorly understood. Using syngeneic mouse model, we recapitulated observed patients, shortened male hosts female hosts. These findings were not immuno-deficient strains such NSG RAG1KO mice, suggesting for system, specifically T cells, differences. Flow cytometry analysis tumor-infiltrating leukocytes revealed that more found tumors, whereas tumors enriched macrophages. Additionally, exhibited high levels inhibitory receptors, functional measured by expression anti-tumor cytokines TNF, IFN-gamma, granzyme B. A bone marrow chimera model (BMC) retained their phenotype hosts, cell behavior was affected environment. Yet on BMC adoptive transfer suggests strong cell-intrinsic effect controlling progression, further supported vitro exhaustion model. Lastly, have progenitor exhausted which led better response anti-PD1 treatment. Collectively, these results suggest both cell-extrinsic factors regulate activity sex-specific manner, providing insights develop therapeutic approaches.