Causal role of 731 immune cells in pancreatic cancer: a Mendelian Randomization study

Background: Pancreatic cancer poses a significant worldwide health challenge. Immune cells are implicated in pancreatic cancer progression and therapy, yet the precise influence of distinct subsets of immune cells remains largely unexplored. The objective of this study is to pinpoint immunophenotypes linked to pancreatic cancer. Methods: Two-sample Mendelian randomization (MR) analysis was employed. Immune phenotypes were retrieved from GWAS, and pancreatic cancer data from the IEU project was split into training and validation sets. Causality was evaluated using the IVW, MR Egger, and weighted median methods. Evaluation included MR-Egger intercept test, funnel plot, leave-one-out analysis for horizontal pleiotropy, and Cochran's Q test for heterogeneity. Estimates from the two sets were combined using the fixed-effects meta-analysis methods. Results: 6 immunophenotypes exhibiting inhibitory effects and 1 showing promoting role. Which is CD20 on IgD⁺ CD38^- naive B cells (95% CI=0.765~0.948, P=0.003, OR = 0.852), CD24 on unsw mem B cells (95% CI=0.861~0.975, P=0.006, OR = 0.917), CD25 on B cells (95% CI=0.859~0.978, P=0.008, OR = 0.917), CD64 on monocyte (95% CI=0.802~0.921, P<0.001, OR = 0.859), CD25 on resting Treg cells (95% CI=0.784~0.957, P=0.005, OR = 0.866), CD39+ CD8br AC Treg cells (95% CI=0.816~0.971, P=0.008, OR = 0.890), HLA DR on B cell (95% CI=1.055~1.206, P<0.001, OR = 1.128) . None immunophenotype displayed potential reverse causality. The reliability of these results was confirmed by the fixed-effects meta-analysis methods. Conclusion: Our study has unveiled causal relationships between immunophenotypes and pancreatic cancer, which can offer guidance for future clinical and basic research endeavors.