Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study

Abstract Background Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. Methods For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. Results We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02–2.55, P = 4.07 × 10 –2 ) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53–0.89, P = 5.74 × 10 –3 ) and CD19 (OR = 0.59, 95%CI = 1.02–2.55, P = 4.07 × 10 –2 ) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01–1.09, P = 1.19 × 10 –2 ) and CD8 + T cells (OR = 1.04, 95%CI = 1.00–1.08, P = 2.83 × 10 –2 ). Conclusions Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.