神经胶质瘤是一种高度致命的脑肿瘤，由具有不同临床轨迹的分子亚型组成。观察性研究表明，免疫反应的变异可能在神经胶质瘤病因学中发挥作用。然而，他们的研究结果不一致，并且由于治疗效果和神经胶质瘤的免疫抑制性质而容易出现反向因果关系。我们应用与血细胞特征相关的遗传变异（p<5×10 -8 ）对 3418 例神经胶质瘤病例和 8156 例对照进行荟萃分析。遗传预测的血小板与淋巴细胞比率 (PLR) 增加与神经胶质瘤风险增加相关（比值比 (OR)=1.25，p=0.005），尤其是在 IDH 突变体中（IDH mut OR=1.38，p=0.007）和 IDH mut 1p/19q 非编码缺失（IDH mut-noncodel OR=1.53，p=0.004）肿瘤。然而，淋巴细胞（IDH mut-noncodel OR=0.70，p=0.004）和中性粒细胞（IDH mut-noncodel OR=0.69，p=0.019；IDH mut-noncodel OR=0.60，p=0.009）计数较高时，神经胶质瘤风险降低。 ，这可能反映了增强免疫监视的遗传倾向。与易感性相反，IDH mut-noncodel 与生存无关；然而，在 IDH mut 1p/19q 共缺失肿瘤中，我们观察到随着基因预测淋巴细胞计数（风险比 (HR)=1.65，95% CI：1.24-2.20）、中性粒细胞（HR=1.49、1.13-）计数的增加，死亡率更高。 1.97) 和嗜酸性粒细胞 (HR=1.59, 1.18-2.14)。血细胞性状的多基因评分也与肿瘤免疫微环境特征相关，在与干扰素信号传导、PD-1 表达和 T 细胞/细胞毒性反应相关的 17 个特征中观察到 IDH 状态的异质性。总之，我们确定了神经胶质瘤的新型免疫介导的易感性机制，具有潜在的疾病管理意义。这项研究表明，外周血细胞计数的遗传决定因素影响亚型特异性神经胶质瘤的易感性和死亡率，并对肿瘤免疫微环境产生潜在影响。这些发现可能对疾病管理有影响。

Glioma is a highly fatal brain tumor comprised of molecular subtypes with distinct clinical trajectories. Observational studies have suggested that variability in immune response may play a role in glioma etiology. However, their findings have been inconsistent and susceptible to reverse causation due to treatment effects and the immunosuppressive nature of glioma. We applied genetic variants associated (p<5×10 -8 ) with blood cell traits to a meta-analysis of 3418 glioma cases and 8156 controls. Genetically predicted increase in the platelet to lymphocyte ratio (PLR) was associated with an increased risk of glioma (odds ratio (OR)=1.25, p=0.005), especially in IDH-mutant (IDH mut OR=1.38, p=0.007) and IDH mut 1p/19q non-codeleted (IDH mut-noncodel OR=1.53, p=0.004) tumors. However, reduced glioma risk was observed for higher counts of lymphocytes (IDH mut-noncodel OR=0.70, p=0.004) and neutrophils (IDH mut OR=0.69, p=0.019; IDH mut-noncodel OR=0.60, p=0.009), which may reflect genetic predisposition to enhanced immune-surveillance. In contrast to susceptibility, there was no association with survival in IDH mut-noncodel; however, in IDH mut 1p/19q co-deleted tumors, we observed higher mortality with increasing genetically predicted counts of lymphocytes (hazard ratio (HR)=1.65, 95% CI: 1.24-2.20), neutrophils (HR=1.49, 1.13-1.97), and eosinophils (HR=1.59, 1.18-2.14). Polygenic scores for blood cell traits were also associated with tumor immune microenvironment features, with heterogeneity by IDH status observed for 17 signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. In summary, we identified novel, immune-mediated susceptibility mechanisms for glioma with potential disease management implications.This study suggests that genetic determinants of peripheral blood cell counts influence subtype-specific glioma susceptibility and mortality, with potential effects on the tumor immune microenvironment. These findings may have disease management implications.