Sex differences in genomics, immune microenvironment and immunotherapy response in adult grade 4 gliomas

Abstract Purpose Sex differences in the prevalence of gliomas have been reported; however, whether there are sex differences in the development and immunotherapy of gliomas remains poorly understood. This study aims to explore sex differences in genomics, immune microenvironment, and immunotherapy response in adult grade 4 gliomas. Methods The clinical and pathological data of 238 patients with adult grade 4 gliomas in our cohort, data of a large tumour immunotherapy cohort (a total of 1512 patients), and several glioma‐related cohorts (a total of 2272 patients) were collected. To comprehensively explore sex‐based differences in grade 4 gliomas, we performed a retrospective analysis, assessed immune‐cell infiltration, and conducted a meta‐analysis. Further characterisation was achieved through immunohistochemistry, Kaplan–Meier survival analysis, Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses to investigate underlying biological mechanisms. Results We found that female grade 4 patients receiving immune checkpoint inhibitor treatment presented a poorer prognosis than male patients, while those receiving non‐immunotherapy exhibited a better prognosis than male patients. Compared to male grade 4 gliomas, female patients had higher levels of tumour‐infiltrating monocyte‐macrophages but lower levels of circulating monocytes. In addition, there were also differences in genomics between female and male grade 4 gliomas. Conclusion There were sex differences in overall survival, immune microenvironment, and genomics in patients with grade 4 gliomas.