Causal relationships between immune cells and common urinary system tumors: A bidirectional analysis of Mendelian randomization

We conducted research on the causal relationships between human immune cells and common urinary system tumors. This study conducted 2-sample Mendelian randomization analyses to determine the causal relationships between immune cell traits and the risk of kidney, bladder, and prostate cancers (PCs). Sensitivity analyses were used to validate the robustness of the results, focusing on pleiotropy and heterogeneity. These findings may inform early diagnosis and personalized immunotherapy for urinary system tumors. Our study identified 12 immune cell phenotypes associated with kidney cancer, including CD127- CD8br absolute cell (AC; odds ratio [OR] = 1.205, 95% confidence interval [CI]: 1.099-1.320, P = 6.73 × 10-5); CD25 on CD39+ activated regulatory T cell (OR = 1.136, 95% CI: 1.037-1.244, P = .006); CD4 on TD CD4+ (OR = 1.102, 95% CI: 1.027-1.182, P = .007); immunoglobulin D (IgD)+ CD38-% lymphocyte (OR = 1.101, 95% CI: 1.031-1.177, P = .004); CD20 on IgD- CD38br (OR = 1.067, 95% CI: 1.017-1.120, P = .008); CD25 on B cell (OR = 1.067, 95% CI: 1.022-1.114, P = .004); HLA DR on B cell (OR = 0.929, 95% CI: 0.882-0.979, P = .006); HLA DR on CD33dim HLA DR+ CD11b- (OR = 0.924, 95% CI: 0.874-0.977, P = .005); HLA DR on CD14+ CD16+ monocyte (OR = 0.947, 95% CI: 0.916-0.980, P = .002); CD62L- plasmacytoid DC %DC (OR = 0.906, 95% CI: 0.850-0.965, P = .002); CD11c on myeloid DC (OR = 0.904, 95% CI: 0.853-0.959, P = 7.38 × 10-4); CD11c on CD62L+ myeloid DC (OR = 0.930, 95% CI: 0.881-0.981, P = .008). Four immune cell phenotypes were associated with bladder cancer, including CD38dim% lymphocyte (OR = 1.081, 95% CI: 1.020-1.145, P = .009); HLA DR+ CD8br AC (OR = 0.940, 95% CI: 0.897-0.985, P = .009); IgD on unsw mem (OR = 0.908, 95% CI: 0.856-0.963, P = .001). In the conventional dendritic cell group, FSC-A on granulocyte (OR = 0.897, 95% CI: 0.836-0.963, P = .003). Six immune cell phenotypes were associated with PC, including CD19 on IgD- CD38- (OR = 1.080, 95% CI: 1.033-1.129, P = 6.21 × 10-4); CD27 on CD20- (OR = 1.040, 95% CI: 1.010-1.072, P = .009); CD86+ plasmacytoid DC %DC (OR = 1.053, 95% CI: 1.013-1.094, P = .009); CD25 on IgD+ CD38- (OR = 0.974, 95% CI: 0.960-0.988, P = 2.59 × 10-4); CD25hi CD45RA+ CD4 not regulatory T cell AC (OR = 0.962, 95% CI: 0.937-0.989, P = .006); CD127 on CD28- CD8br (OR = 0.952, 95% CI: 0.920-0.984, P = .004). Our study, utilizing Mendelian randomization genetic methods, has demonstrated the causal associations between immune cell phenotypes and kidney cancer, bladder cancer, and PC, providing guidance for future clinical diagnosis and treatment of these 3 malignant tumors of the urinary system.