IMMU-24. TESTOSTERONE FUNCTIONS AS A TUMOR SUPPRESSOR IN GLIOBLASTOMA

Abstract A sex difference in the incidence and outcome of patients with glioblastoma (GBM), most common primary malignant brain tumor, has been well established, as male experience a worse prognosis. However, contribution hormones to anti-tumor immunity not fully explored. To test this, we orthotopically implanted syngeneic mouse GBM cells into mice after castration or sham surgery assess survival differences. Castrated immune-competent succumbed tumors significantly faster than group, this was rescued by exogenous testosterone administration. This finding further corroborated that blockade androgen signaling using enzalutamide reproduced effect shortened survival. In contrast, on immunocompromised mice, NSG RAG1KO, resulted no compared animals, suggesting role for immune system. Flow cytometry analysis tumor-infiltrating revealed decreased cytokine production T NK from castrated while found cell infiltration. Flank tumor experiments suggested brain-specific regulation recruitment, growth delayed increased infiltration CD8+ cell. It is noted observed lymph nodes flank model. Surprisingly, mass spectrometry serum upregulated levels circulating corticosterone regardless presence, may induce systemic immunosuppression regulate via upregulation glucocorticoids. Taken together, our data demonstrate regulates immunity, possibly glucocorticoids, ultimately affects growth. Given level aged males higher risk GBM, these findings suggest potential therapeutic intervention GBM.