Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2024 Jul;15(21):1673-1680. doi: 10.1111/1759-7714.15394. Epub 2024 Jun 22.
Lung adenocarcinoma (LUAD) is the most common type of lung cancer and closely associated with the immune system. Emerging evidence suggests that blood immune cell phenotypes in patients with LUAD may undergo alterations. Nevertheless, the limited amount of relevant research makes it difficult to understand the causal links between LUAD and changes in the immune cells. This study aimed to reveal the potential causal relationships between 731 immune cell phenotypes and LUAD.
A bidirectional two-sample Mendelian randomization (MR) analysis was used to clarify causal relationships. Four types of immune phenotypes, absolute cell counts, relative cell counts, median fluorescence intensities (MFIs) of surface antigens, and morphological parameters, were investigated in this study. Heterogeneity tests, horizontal pleiotropy tests, and leave-one-out analyses were performed to validate the reliability of our study.
A total of 26 immune cell characteristics were identified as contributing to the occurrence of LUAD. Memory B cells, IgDCD38 cells, CD4 regulatory T cells (Tregs), and plasmacytoid dendritic cells (DCs) may play a role in the development of LUAD. Through reverse MR, our study discovered that the presence of LUAD also induced changes in the expression levels of 16 immune cell traits involving specific surface markers and various types of immune cells, some of which pertain to antigen presentation and immune activation processes.
Our study demonstrated causal links between several immune cell phenotypes and LUAD, thereby providing indications of the potentially oncogenic physiological state and early screening biomarkers for future research.
肺腺癌（LUAD）是最常见的肺癌类型，与免疫系统密切相关。新出现的证据表明，LUAD 患者的血液免疫细胞表型可能发生改变。然而，相关研究的数量有限，难以理解 LUAD 与免疫细胞变化之间的因果关系。本研究旨在揭示 731 种免疫细胞表型与 LUAD 之间的潜在因果关系。
采用双向两样本 Mendelian 随机化（MR）分析来阐明因果关系。本研究调查了四种免疫表型，即绝对细胞计数、相对细胞计数、表面抗原的中位荧光强度（MFI）和形态学参数。进行了异质性检验、水平多效性检验和逐一排除分析，以验证我们研究的可靠性。
共有 26 种免疫细胞特征被确定为导致 LUAD 发生的因素。记忆 B 细胞、IgDCD38 细胞、CD4 调节性 T 细胞（Tregs）和浆细胞样树突状细胞（DCs）可能在 LUAD 的发展中起作用。通过反向 MR，我们的研究发现 LUAD 的存在也诱导了 16 种免疫细胞特征的表达水平发生变化，这些特征涉及特定的表面标志物和各种类型的免疫细胞，其中一些与抗原呈递和免疫激活过程有关。
本研究证明了几种免疫细胞表型与 LUAD 之间存在因果关系，从而为潜在的致癌生理状态和未来研究的早期筛选生物标志物提供了依据。
