■胶质母细胞瘤(GBM)是一种高度恶性的脑肿瘤,免疫细胞在其启动和发展中起着至关重要的作用。免疫系统的细胞成分,包括各种类型的淋巴细胞,巨噬细胞,和树突状细胞,其中,与GBM进行复杂的互动。然而,这些相互作用的确切性质仍有待最终确定。
■在这项研究中,我们进行了一项全面的双样本孟德尔随机化(MR)分析,以阐明免疫细胞特征与GBM发病率之间的因果关系.利用公开的遗传数据,我们调查了731种免疫细胞特征与GBM风险之间的因果关系.随后,我们进行了反向孟德尔随机化分析以排除反向因果关系.最后,结论免疫细胞的三种亚型与GBM之间存在单向因果关系。采用综合敏感性分析来验证结果的稳健性,异质性,以及水平多效性的存在。为了提高我们结果的准确性,我们同时对它们进行贝叶斯分析。
■进行MR分析后,我们确定了10种对抗胶质母细胞瘤的免疫表型,FSC-A对自然杀伤T细胞的保护作用最强(OR=0.688,CI=0.515-0.918,P=0.011)。此外,我们发现了11种促进GBM发病率的免疫细胞亚型,包括CD62L-HLADR+单核细胞百分比(OR=1.522,CI=1.004-2.307,P=0.048),CD4+CD8+T细胞白细胞百分比(OR=1.387,CI=1.031-1.866,P=0.031)。在实施反向MR分析之后,其中胶质母细胞瘤作为暴露变量,结果包括21种靶免疫细胞亚型,我们发现只有三种细胞亚型(CD45在CD33+HLADR+CD14dim,CD33+HLADR+绝对计数,和IgD+CD24+B细胞绝对计数)与胶质母细胞瘤表现出单向因果关联。
■我们的研究从基因上证明了免疫细胞和GBM之间的密切关系,指导未来的临床研究。
UNASSIGNED: Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system\'s cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined.
UNASSIGNED: In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis.
UNASSIGNED: After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma.
UNASSIGNED: Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.