Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study

Area of Science:

• Immunology
• Genetics
• Oncology

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
• Immunotherapy offers new hope for HCC patients.
• Understanding immune cell roles in HCC is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the causal relationship between 731 immune cell phenotypes and HCC risk.
• To identify potential drug targets for HCC.
• To explore the underlying mechanisms of HCC development.

Main Methods:

• Two-sample Mendelian Randomization (MR) analysis was used to assess causal links between immune cell traits and HCC.
• Extensive sensitivity analyses were performed to ensure the robustness of the MR findings.
• Single-cell RNA sequencing (scRNA-seq) was employed to analyze immune cell phenotypes and their interactions in HCC.

Main Results:

• Five immune cell phenotypes were associated with increased HCC risk: B cell % CD3- lymphocyte, CD25 on IgD+ B cells, HVEM on TD CD4+ T cells, CD14 on CD14+ CD16- monocytes, and CD4 on CD39+ activated Tregs.
• Cellular phenotypes related to BAFF-R expression showed a protective effect against HCC.
• Single-cell sequencing revealed significant immune cell communication and metabolic activity differences in HCC.

Conclusions:

• MR and scRNA-seq identified potential associations between specific immune cell phenotypes and HCC.
• The study highlights complex molecular interactions among immune cell phenotypes in HCC.
• Findings may help overcome limitations of current mono-antibody therapies for HCC.