Yang Bo, Li Zhenyu, Li Peiliang, Liang Bo, Liu Yuhan, Feng Enshan
Department of Neurosurgery, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Department of Neonatology , The First Hospital of Jilin University, Changchun, China.
BMC Neurol. 2025 Jan 8;25(1):12. doi: 10.1186/s12883-024-04015-1.
Malignant brain tumors are among the most lethal cancers. Recent studies emphasized the crucial involvement of the immune system, especially T cells, in driving tumor progression and influencing patient outcomes. The emerging field of immunometabolism has shown that metabolic pathways play a pivotal role in regulating immune responses within the tumor microenvironment. This study aims to clarify the relationships between specific T cell phenotypes, circulating metabolites, and malignant brain tumors.
We utilized a multiple mendelian randomization approach to investigate the associations between T cell phenotypes and malignant brain tumors, as well as the role of plasma metabolites in mediating these interactions. Instrumental variables were selected based on stringent criteria, and multiple mendelian randomization methods were utilized to identify causal pathways and metabolites potentially mediating these effects.
Our analysis identified significant associations between seven distinct T cell phenotypes, including various CD8 + and regulatory T cell subsets, and the presence of malignant brain tumors. We also identified 87 plasma metabolites correlated with these tumors. Notably, metabolites such as octadecanedioylcarnitine (C18-DC) and eicosanedioate (C20-DC) were implicated in modulating the risk of developing malignant brain tumors. Furthermore, metabolites such as 5-dodecenoate (12:1n7) and arachidonate (20:4n6) were found to influence tumor risk, particularly in relation to CD28 - CD8 + T cells.
The study identifies key T cell phenotypes and plasma metabolites involved in the pathogenesis of malignant brain tumors, offering potential biomarkers and therapeutic targets for future interventions.
恶性脑肿瘤是最致命的癌症之一。最近的研究强调了免疫系统，尤其是T细胞，在推动肿瘤进展和影响患者预后方面的关键作用。免疫代谢这一新兴领域表明，代谢途径在调节肿瘤微环境中的免疫反应中起关键作用。本研究旨在阐明特定T细胞表型、循环代谢物与恶性脑肿瘤之间的关系。
我们采用多重孟德尔随机化方法来研究T细胞表型与恶性脑肿瘤之间的关联，以及血浆代谢物在介导这些相互作用中的作用。根据严格标准选择工具变量，并利用多重孟德尔随机化方法来确定潜在介导这些效应的因果途径和代谢物。
我们的分析确定了七种不同的T细胞表型之间的显著关联，包括各种CD8 +和调节性T细胞亚群，以及恶性脑肿瘤的存在。我们还确定了87种与这些肿瘤相关的血浆代谢物。值得注意的是，诸如十八烷二酰肉碱（C18-DC）和二十烷二酸（C20-DC）等代谢物与调节发生恶性脑肿瘤的风险有关。此外，发现诸如5-十二碳烯酸（12:1n7）和花生四烯酸（20:4n6）等代谢物会影响肿瘤风险，特别是与CD28-CD8 + T细胞有关。
该研究确定了参与恶性脑肿瘤发病机制的关键T细胞表型和血浆代谢物，为未来干预提供了潜在的生物标志物和治疗靶点。
