Exploring the Role of Immune Cells in Glioma: Causal Associations and Clinical Implications

Background: Gliomas, the predominant malignant neoplasm of the central nervous system, are notorious for their recurrence and unfavourable prognosis. Immune cells play a pivotal role in the progression of various solid tumors, including gliomas. This study aims to explore the potential causal effect of immune cells on the risk of glioma and the association between immune cells and clinical characteristics in glioma. Materials and Methods: This study used the public genome-wide association studies (GWAS) summary data of 731 immune cell traits and gliomas to perform two-sample Mendelian randomization (MR) analysis. The MR analysis primarily employed the inverse variance weighting (IVW) method, supplemented by three additional methods, alongside comprehensive pleiotropy and heterogeneity analyses. In addition, 151 glioma samples were collected for RNA-Seq to construct the CSUXY cohort, and RNA-Seq data and clinical information of 588 glioma samples in the TCGA cohort were collected. The associations between immune cell abundance and clinical characteristics and drug sensitivity of each sample were inferred in the two cohorts. Results: Based on the IVW method, this study identified potential causal associations between 16 immune cell traits and the risk of glioma. The other three MR analysis methods had consistent causal directions with the IVW method and there was no horizontal pleiotropy and heterogeneity. Higher levels of immune cell infiltration were observed in IDH wild-type and 1p19q non-codel gliomas compared to IDH mutant and 1p19q codel gliomas across both the CSUXY and TCGA cohorts. In addition, the abundance of immune cells was also associated with the grade, histological subtype and prognosis of gliomas. Finally, this study also identified broad associations between immune cell abundance and drug sensitivity in glioma. Conclusion: This study supports the causal effects of specific immune cell traits on glioma and confirms the associations between immune cells and clinical characteristics, as well as drug sensitivity in glioma, providing evidence for the development of immune cell-based biomarkers.