Sexual dimorphism of the immune system predicts clinical outcomes in glioblastoma immunotherapy: A systematic review and meta-analysis

BACKGROUND: Biological differences based on sex have been documented throughout the scientific literature. Glioblastoma (GBM), 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 exists. METHOD: We analyzed genomic data, as well as clinical trials, to delineate the effect of sex on the immune system and GBM outcome following immunotherapy. RESULTS: We found that in general females possess enriched immunological signatures on gene set enrichment analysis, which also stratified patient survival when delineated by sex. Female GBM patients treated with immunotherapy had a statistically significant survival advantage at the 1-year compared to males (relative risk [RR] = 1.15; P = .0241). This effect was even more pronounced in vaccine-based immunotherapy (RR = 1.29; P = .0158). CONCLUSIONS: Our study shows a meaningful difference in the immunobiology between males and females that also influences the overall response to immunotherapy in the setting of GBM.