TMIC-02. SEX DIFFERENCES IN IMMUNE RESPONSE IN A MURINE GLIOBLASTOMA RESECTION MODEL CONFER A FEMALE SURVIVAL ADVANTAGE

Abstract

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor with a median survival of 15-20 months, despite standard of care treatment, which includes surgical resection, radiation, and chemotherapy. GBM is 1.6 times more common in males and overall survival can be up to 10 months shorter in males. Females are more responsive to standard of care therapy, but the mechanism behind these differences is not clear. The immune system is known to be suppressed in GBM patients, and recent studies have found sex differences in immune response. While pre-clinical GBM models are used to interrogate pathophysiology and response to therapeutic interventions, few of these models include surgical resection, despite its role in the standard of care for patients and as a defining therapy in prolonging survival. We developed a pre-clinical GBM resection model to evaluate whether there is a sex bias in survival and to interrogate sex-specific immune changes after surgery. We found that C57BL/6 mice implanted with syngeneic GBM cells demonstrate a sex bias after surgical resection, with males surviving for a median of 24 days compared to 33 days for females. To understand how the immune response is affected by surgical resection in males and females with GBM, we performed flow cytometry to characterize the immune phenotype and found that female mice who underwent resection of their tumors had significantly higher levels of CD4+ T cells in their resection cavity than male mice who underwent resection. The immune phenotype will be further characterized over time to evaluate how it evolves in each sex. These data support prior observations that the mechanisms of immunosuppression are different in males and females. They further underscore the complexity of sex bias in GBM and the need to account for surgical resection and sex in pre-clinical models to investigate next-generation therapeutic strategies.