The immune cells causative role in lung cancer: Mendelian randomization study

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• Lung cancer (LC) is a leading cause of cancer mortality in China, with rising incidence and mortality rates.
• Disparities in immune cell profiles exist between LC patients and healthy individuals, but causal links are uncertain.
• Mendelian randomization (MR) is employed to investigate potential causal associations between immune cells and LC risk.

Purpose of the Study:

• To explore the potential causal relationship between various immune cell types and the risk of developing lung cancer.
• To identify specific immune cell populations that may either protect against or promote lung cancer development.

Main Methods:

• Utilized genome-wide association study (GWAS) data for immune cells (n=731) and lung cancer (n=492,803).
• Employed inverse variance weighting (IVW) as the primary analytical strategy, with sensitivity analyses including leave-one-out, heterogeneity, and pleiotropy tests (MR-Egger, MR-PRESSO).
• Extracted genetic loci associated with 731 immune cell types as instrumental variables.

Main Results:

• Identified significant associations between 18 distinct immune cell types and lung cancer risk.
• Seven immune cell types, including specific B cell subsets and T cell populations (e.g., CD39+ resting CD4 regulatory T cell), showed a protective effect against LC.
• Eleven immune cell populations were positively associated with increased LC risk, while reverse MR indicated 2 immune cell types (e.g., CD25 on IgD-CD27-B cell) positively correlated with cancer development.

Conclusions:

• Specific immune cell subsets play critical roles in either promoting or suppressing lung cancer initiation and progression.
• Findings provide novel insights into the biological mechanisms of lung cancer development.
• Identified immune cell subsets offer potential targets for novel preventive, diagnostic, and therapeutic strategies for lung cancer.