# Association of Immune Cells, Inflammatory Cytokines, and Lung Cancer: A Mediating Mendelian Randomization Study

## TL;DR

This study explores how immune cells and inflammatory cytokines influence lung cancer risk using genetic data, revealing potential new targets for diagnosis and treatment.

## Contribution

The study identifies causal and mediating relationships between immune-cell markers, cytokines, and specific lung cancer subtypes using Mendelian randomization.

## Key findings

- BAFF-R expression in IgD+ CD24+ B cells increases lung adenocarcinoma risk, mediated by macrophage migration inhibition factor (MIF).
- CD39 expression on CD4 Tregs is linked to small-cell lung cancer risk, mediated by IL-2 and IL-6.
- CD28 expression on CD39+ CD4+ T cells correlates with lung squamous cell carcinoma risk, inversely mediated by IL-16.

## Abstract

Lung cancer oncogenesis involves interactions between immune cells and inflammatory cytokines. However, their causal relationships and mediating mechanism remain unclear.

Using a mediating Mendelian randomization (MR) approach, we analyzed genome-wide association study (GWAS) data for 731 immune-cellular phenotypes, 41 cytokines, and eight related lung cancer phenotypes.

BAFF-R expression in IgD+ CD24+ B cells was positively associated with lung adenocarcinoma (LUAD) risk (odds ratio [OR], 1.0168 [95% confidence interval [CI], 1.0006–1.0332]), mediated by macrophage migration inhibition factor (MIF) with a mediation proportion of 14.2% (95% CI, 0.00007–0.0046). CD39 expression on secreting CD4 Tregs was related to an increased risk of small-cell lung cancer (SCLC) (OR, 1.0306 [95% CI, 1.0006–1.0616]), mediated by interleukin (IL)-2 and IL-6 with mediation proportions of 8.43% (95% CI, 0.00005−0.005) and 5.1% (95% CI, 0.00006–0.003), respectively. CD28 expression on CD39+ CD4+ T cells was positively correlated to lung squamous cell carcinoma (LUSC) risk (OR, 1.0335 [95% CI, 1.009–1.0586]), inversely mediated by IL-16 (95% CI, −0.01 to −0.0003).

These findings reveal the associations between immune cells, inflammatory cytokines, and lung cancer risk, providing insights into cancer diagnosis and treatment.