Abstract
Abstract Biological differences based on sex have been documented throughout scientific literature. Glioblastoma, the most common primary malignant brain tumor in adults, has a male sex incidence bias, however, no clinical trial data examining differential effects of treatment between sexes currently exist. We analyzed genomic data, as well as clinical trials, to delineate the effect of sex on the immune system and glioblastoma outcome following immunotherapy. We found that, in general females possess enriched immunological signatures on gene set enrichment analysis, that also stratified patient survival when delineated by sex. Female glioblastoma patients treated with immunotherapy had a statistically significant survival advantage at the 1-year compared to males (RR = 1.15; p = 0.0241). This effect was even more pronounced in vaccine-based immunotherapy, (RR = 1.29; p = 0.0158). Our study shows a meaningful difference in the immunobiology between males and females that also influences overall response to immunotherapy in the setting of glioblastoma. Our study adds to a growing body of literature examining sex differences in male and female immunology. We demonstrate both using large scale omic data sets, as well as clinical trials, that female sexually dimorphic genes are tied to immunological responses, and that females have better outcomes during GBM immunotherapy treatments. This data is critical to better inform treatment practices and further crystalizes the need for balanced trial design and prospective reporting of sex as a variable across all GBM clinical trials.
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