COPD-Lung Cancer Link: Regulatory T Cells as Intermediaries

Observational studies highlight a link between chronic obstructive pulmonary disease (COPD) and lung cancer (LC), suggesting potential immune system interactions as causative factors. Despite this, the precise causal association and immune-mediated mechanisms between COPD and LC remain unclear.

Dengfeng Zhang and the team aimed to elucidate the causal association and immune-mediated mechanisms underlying the relationship between COPD and LC, potentially opening avenues for therapeutic interventions.

Researchers performed an inclusive analysis utilizing a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and LC. Additionally, an examination was conducted on whether immune cell signals were causally related to LC and whether COPD was causally associated with immune cell signals.

Furthermore, through a two-step MR, the mediating effects of immune cell signals in the causal association between COPD and LC were investigated. Leveraging publicly available genetic data, the analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with LC, and 731 immune cell signatures of European ancestry. Additionally, to validate the findings, single-cell transcriptome sequencing analysis was conducted on COPD, LC, and control samples.

A causal association was identified between COPD and LC (OR = 1.63, 95% CI = 1.31-2.02, P-value < 0.001). Additionally, a causal link was observed between COPD and regulatory T cells (OR = 1.19, 95% CI = 1.01-1.40, P-value < 0.05), along with a causal association between regulatory T cells and LC (OR= 1.02, 95% CI = 1.002-1.045, P-value < 0.05).

Moreover, the two-step MR analysis demonstrated COPD’s association with LC by mediating regulatory T cells. These findings were further corroborated via single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and LC.

The study concluded that combining single-celled immune cell data with two-sample MR revealed a significant causal association between COPD and lung cancer. Regulatory T cells were identified as playing an intermediary role in this association.

This novel approach significantly advances the understanding the relationship between COPD and lung cancer, offering potential insights for future therapeutic strategies.

This study was sponsored by the Science and Technology Plan Project of Hebei Province and the Hebei Provincial Government sponsored the project of training excellent talents in clinical medicine.

Source: https://pubmed.ncbi.nlm.nih.gov/38605291/

Zhang D, Liu H, Zhao F, et al. (2024). “Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration. BMC Cancer.” 2024 Apr 11;24(1):453. doi: 10.1186/s12885-024-12076-1. PMID: 38605291; PMCID: PMC11010300.