The causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomization (MR).

Objective: Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC.

Method: We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses.

Results: We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC.

Conclusion: Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC.