Association of immune cells and the risk of esophageal cancer: A Mendelian randomization study in a East Asian population

Abstract

Immunotherapy has been used in esophageal cancer (EC), but the causal relationship between EC and immune cells is not clear. Although the cellular phenotype has been reported as a biomarker for immunotherapy, the biomarker studies for immunotherapy in EC still face great challenges. Comprehensive 2-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and EC in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and EC risk. EC had no statistically significant effect on immunophenotypes. Nine immunophenotype types were positively associated with the risk of EC: CD20-%B cell, CD20% lymphocytes, CD25 on IgD- CD27-, CD25 on IgD+ CD24+, CD27 on IgD+ CD24+, CD28+ CD45RA- CD8br AC, CD3 on TD CD8br, IgD-CD38dim%B cells, and Mo MDSC AC. In addition, a total of 15 immunophenotypes were identified as causally associated with EC. IgD+ CD38- %B cell, IgD- CD24- %lymphocyte, CD19 on IgD- CD38dim, CD20 on IgD+ CD24+, CD62L-myeloid DC AC, CD4+ AC, Lymphocyte %leukocyte, CD3 on HLA-DR+ T cell, CD3 on CD45RA- CD4+, HVEM on naive CD4+ AC, HVEM on CD45RA- CD4+, CD4 on TD CD4+, CD4 on CD4 Treg, and CD4 on CD39+ resting Treg, and CD4 on activated & secreting Treg. Our study has demonstrated the close connection between immune cells and EC by genetic means, thus providing guidance for future clinical research.