Abstract
OBJECTIVE: We aimed to identify potential causal immune cells and their phenotypes in benign and malignant thymic tumors from the FinnGen database using Mendelian randomization (MR). METHODS: A two-sample MR approach was employed to evaluate the causal associations between 731 immune cell traits and the risk of benign and malignant thymomas using publicly available genetic datasets. Immune traits analyzed included median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP). Robustness of findings was assessed through sensitivity analyses, ensuring minimal heterogeneity and horizontal pleiotropy. RESULTS: Four immune cell phenotypes, including CCR2 on CD14+ CD16+ monocytes (95% CI: 1.163-1.775, P = 0.0007) and transitional AC (95% CI: 1.176-3.232, P = 0.0095), were causally associated with benign thymomas and identified as risk factors. Conversely, naive-mature B cell AC (95% CI: 0.438-0.887, P = 0.0087) and natural killer (NK) AC (95% CI: 0.237-0.812, P = 0.0087) displayed protective effects. For malignant thymomas, seven immune phenotypes, including Memory B cell %B cell (95% CI: 1.160-2.242, P = 0.0045), were linked as risk factors, while three, such as IgD+ CD24- %B cells (95% CI: 0.438-0.868, P = 0.0055), exhibited protective associations. Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Using genetic methodologies, we identified a robust link between immune cells and both benign and malignant thymic tumors. This study highlights the distinct immune phenotypes between benign and malignant thymic tumors, shedding light on their immunological mechanisms and suggesting new avenues for clinical immunotherapy.