IMMU-71. Females benefit more from surgical resection in an immune-dependent manner in a preclinical glioblastoma model

Abstract Glioblastoma (GBM) is 1.6 times more common in males who also have a shorter overall survival than females. The immune system is suppressed in GBM, and studies have found sex differences in the immune response. While preclinical GBM models are used to interrogate GBM pathophysiology, few include resection, despite its role in the standard of care. The aim of this study was to determine sex differences in surgical resection in GBM. We developed a preclinical GBM resection model in which mice were implanted with syngeneic GBM cells and underwent tumor resection. RNA sequencing was used to characterize transcriptional changes, and immune phenotype after surgery was investigated via flow cytometry. In an immunocompetent model, females survived longer than males after resection, but there were no significant transcriptional differences found between the sexes. Interestingly, the sex bias in survival was abrogated in immunocompromised mice. Immunocompetent female mice who underwent resection had higher levels of immune cell infiltration in their resection cavity while males had decreased T regulatory (Treg) cells post-resection. When Tregs were depleted via the utilization of Foxp3DTR mice, the sex bias in survival was abrogated. Analysis of GBM patients in the National Cancer Database found that while female patients survive longer than male patients after resection, there is no sex bias in survival after biopsy alone. These results demonstrate a sex bias in survival after resection that is immune-dependent. Tregs may serve a protective role post-operatively and should be further studied to understand how and when they become important for survival. These data underscore the complexity of sex bias and the immune system in GBM and the need to account for biological sex and resection in preclinical models to investigate next-generation therapies.