Characterization of circulating immune profiles associated with specific COPD phenotypes and concurrent lung cancer status

Chronic obstructive pulmonary disease (COPD) and emphysema are independent risk factors for lung cancer (LC), potentially linked by shared systemic immune alterations. This cross-sectional study investigates the associations between circulating helper T (Th) cell subsets, immunosuppressive populations, and antigen-presenting cells (APCs) across distinct COPD phenotypes and concurrent LC status. Sixty-four subjects were enrolled ( n = 16 per group): COPD without emphysema (COPD-no-E), COPD with emphysema (COPD-E), COPD with emphysema and LC (COPD-E-LC), and healthy smoker controls (CS). Peripheral blood Th cell subsets, regulatory T (Treg) cells, monocytic-myeloid-derived suppressor cells (M-MDSC), and plasmacytoid dendritic cells (pDCs) were enumerated by flow cytometry. Activation status in APC was evaluated via HLA-DR Mean Fluorescence Intensity (MFI). Plasma cytokines were analyzed using Luminex xMAP technology. Linear discriminant analysis and random forest models were applied for exploratory feature prioritization. Emphysema-associated cohorts (COPD-E and COPD-E-LC) demonstrated lower HLA-DR expression on monocytes and pDCs, with the lowest values observed in the LC group. Conversely, the COPD-no-E group exhibited significantly higher frequencies of Treg cells, M-MDSC phenotype, Th17 and CD194 − CD196 + cell subsets, alongside elevated plasma IL-13. In exploratory multivariate analyses, pDC frequency, M-MDSC percentages, and HLA-DR profiles emerged as the primary mathematical features contributing to group characterization. COPD phenotypes exhibit significant systemic immunological heterogeneity. The non-emphysematous phenotype is associated with expansion of circulating Treg cells and M-MDSC-like subset. Conversely, emphysema is characterized by down-regulated HLA-DR expression on circulating APC, reflecting an altered activation state. These distinct profiles demonstrate that assessing the clinical phenotype is essential for accurately understanding immune variations in COPD and LC.