CC-Chemokine Ligand 18 Is an Independent Prognostic Marker in Lymph Node-positive Non-small Cell Lung Cancer

Abstract

Background/aim: Tumor-associated macrophages (TAMs) are key players in the immune response in non-small cell lung cancer (NSCLC) and the main producers of CC-chemokine ligand 18 (CCL18). Our study aimed to analyze the clinical significance of CCL18 expression by TAMs in NSCLC.

Material and methods: Tissue multi-arrays from 243 non-selected patients with NSCLC were constructed. Immunohistochemical double staining for CD68 and CCL18 was performed and the number of CD68⁺, as well as CCL18⁺/CD68⁺ macrophages determined.

Results: Comparison of early to advanced lung adenocarcinoma showed significantly more frequent CD68⁺ as well as CD68/CCL18 double-positive macrophages in advanced disease (p=0.03 and p=0.04). Multivariate analysis revealed a higher proportion of double-positive macrophages to be an independent prognosticator in lymph node-positive NSCLC (hazard ratio(HR)=0.6, 95% confidence interval(CI)=0.35-0.86, p=0.009).

Conclusion: In advanced lung adenocarcinoma, infiltration of CCL18⁺ TAMs was increased and higher expression of CCL18 by TAMs was associated with a favorable prognosis in lymph-node positive NSCLC.

Keywords: CCL18; NSCLC; TAMs; immune response; non-small-cell lung cancer; prognostic factors; tumor microenvironment; tumor-associated macrophages.