Emphysema Shapes a Pro-Inflammatory Immune Microenvironment in Pulmonary Adenocarcinoma: A Pilot Immune Transcriptomic Profiling Study.

Authors

Jeong Uk Lim, Seohyeon Kim, Tai Joon An, Young Jo Sa, Hyo Rim Kim, Chan Kwon Park, Hyoung Kyu Yoon, Tae-Jung Kim

Published in

International journal of molecular sciences. Volume 27. Issue 9. Apr 29, 2026. Epub Apr 29, 2026.

Abstract

Emphysema is a well-recognized risk factor for lung cancer; however, its influence on the immunologic tumor microenvironment in lung adenocarcinoma remains poorly defined. In this pilot, hypothesis-generating study, immune-related gene expression profiling was performed using archival formalin-fixed paraffin-embedded tumor specimens from 12 patients with lung adenocarcinoma, including the Never-smoker group (never-smokers without emphysema; n = 4), the Smoker 1 group (smokers without emphysema; n = 3), and the Smoker 2 group (smokers with CT-defined emphysema; n = 5). Expression of 770 immune-related genes was analyzed using the nCounter PanCancer IO 360 Panel (NanoString Technologies, Seattle, WA, USA). Compared with the Never-smoker group, tumors from the Smoker 1 group showed marked upregulation of SFRP1, SERPINB5, and IL6, whereas tumors from the Smoker 2 group exhibited increased expression of KIR2DL3, BLK, and WNT2B. Relative to the Smoker 1 group, the Smoker 2 group demonstrated significant upregulation of MMP7, TDO2, and CCL18. Pathway enrichment analysis revealed cytokine-cytokine receptor interaction as the most prominently enriched pathway in both smoker groups, while the IL-17 signaling pathway was preferentially enriched in the Smoker 2 group. In addition, diffusing capacity for carbon monoxide showed significant correlations with immune-related genes including IL-6 and IL-6R. Collectively, these preliminary findings suggest that lung adenocarcinoma arising in emphysematous lungs may be characterized by a distinct pro-inflammatory immune microenvironment. Given the small sample size and potential confounders, these results should be regarded as hypothesis-generating. Emphysema-associated immune remodeling may nevertheless represent an important biological factor worthy of validation in larger, independent cohorts.

PMID:
42123542
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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