The causal effects of immune cells on pancreatic cancer: A 2‑sample Mendelian randomization study

Leveraging publicly available genetic datasets, we conducted a comprehensive 2-sample Mendelian randomization (MR) analysis to explore the causal links between 731 immunophenotypes and the risk of pancreatic cancer (PC). To ensure the robustness of our findings, extensive sensitivity analyses were performed, evaluating stability, heterogeneity, and potential horizontal pleiotropy. Our analysis pinpointed 24 immunophenotypes significantly associated with the risk of PC. Notably, phenotypes such as CD4+ CD8dim %leukocyte (OR = 0.852, 95% CI = 0.729-0.995, P = .0430) and HLA DR+ CD4+ AC (OR = 0.933, 95% CI = 0.883-0.986) in TBNK were inversely correlated with PC risk. Conversely, phenotypes like CD28 on CD45RA- CD4 non-Treg (OR = 1.155, 95% CI = 1.028-1.297, P = .016) and CD25 on activated Treg (OR = 1.180, 95% CI = 1.014-1.374, P = .032) in Treg cells, among others, exhibited a positive correlation. These insights offer a valuable genetic perspective that could guide future clinical research in this area.