Immune cell phenotype in endometrial cancer: from biological significance to clinical utility using Mendelian randomisation analysis

We investigated the relationship between immune cells and endometrial cancer by conducting a two-sample bidirectional Mendelian randomisation (MR) analysis. MR uses genetic variation as an instrumental variable to study the causal effects of exposure on observed data outcomes. We conducted a dual-sample MR analysis to investigate the causal relationship between 731 immune cell phenotypes and endometrial cancer (EC). The weighted-median method and inverse variance weighted method MR were mainly used, and the <i>p</i>-value was corrected with the Benjamini-Hochberg procedure. The forward MR analysis revealed a causal relationship between EC and eight immune-cell phenotypes. The reverse MR analysis identified two immune-cell phenotypes with a potential causal effect on EC, with additional subtype-specific associations observed for endometrioid and non-endometrioid histology. Our study demonstrated a causal relationship between immune cells and EC, thereby providing guidance for the development of future immunoregulatory therapeutic strategies. Endometrial cancer (EC), a type of cancer that begins in the lining of the uterus, may be influenced by the immune system. In this study, we used a genetic analysis method called Mendelian randomisation to explore whether certain types of immune cells play a role in causing or being affected by endometrial cancer. By analysing genetic data from large studies, we examined over 700 immune cell traits to see if they are linked to EC. We found that some immune cell types may be influenced by having EC, while a few others might actually contribute to the development of the disease. Interestingly, these relationships were different depending on the specific type of endometrial cancer. Our findings suggest that the immune system and endometrial cancer affect each other in complex ways. This information may help guide future research and lead to new treatments that target the immune system to better manage or prevent this type of cancer.