Immunoprofiling bronchoalveolar lavage cells reveals multifaceted smoking-associated immune dysfunction

Area of Science:

• Immunology
• Pulmonary Medicine
• Oncology

Background:

• Bronchoalveolar lavage (BAL) is an underutilized resource for identifying pulmonary disease biomarkers.
• The role of BAL leukocyte frequencies and phenotypes in lung cancer research remains unclear.
• Investigating smoking's impact on pulmonary immunity using BAL leukocytes is crucial, as smoking is a primary lung cancer risk factor.

Purpose of the Study:

• To explore the utility of BAL leukocytes as biomarkers for assessing smoking's impact on pulmonary immunity.
• To investigate how smoking status influences the frequencies and phenotypes of immune cells within the airways.

Main Methods:

• An observational study analyzed BAL samples from 119 lung cancer screening participants.
• Conventional and spectral flow cytometry were employed for comprehensive immune cell profiling.
• Multivariate analysis considered age, sex, cancer diagnosis, and smoking status.

Main Results:

• Current and former smokers showed increased myeloid-derived suppressor cells and PD-L1 macrophages compared to never-smokers.
• Reduced frequencies of cytotoxic CD8 T-cells and CD4 helper T-cells were observed in smokers.
• Increased expression of immune checkpoints (PD-1, LAG-3) and regulatory T-cells (Tregs) were noted in smokers.
• BAL sample stability under cryostorage supports their use in clinical trials.

Conclusions:

• Smoking is linked to elevated immune dysfunction markers in the airways, detectable via BAL.
• These immune alterations may create an environment conducive to lung cancer development and progression.
• BAL analysis offers a valuable tool for lung cancer research and clinical trials.