Prognostic impact and gene expression analysis of peri-tumoral alveolar macrophage in resected lung adenocarcinoma.

The prognostic significance and role of extratumoral alveolar macrophages (exAMs) in lung adenocarcinoma (LUAD) patients remain unknown. In this study, we investigated the prognostic impact and gene expression of exAMs in LUAD patients. The density of alveolar macrophages (AMs) in the peri-tumoral lung field (p-exAMs) and distant lung field (d-exAMs) was evaluated in 217 LUAD patients with lymph node metastasis. Patients with high p-exAMs showed significantly shorter recurrence-free (RFS) and shorter overall survival (OS) than those with low p-exAMs (p = 0.02 and p = 0.03, respectively), whereas there was no survival difference between patients with high d-exAMs and those with low d-exAMs. Multivariate analysis revealed that high p-exAMs was an independent predictive factor for RFS (HR: 1.54; 95% confidence interval [CI]:1.10-2.16; p = 0.01). Later, we collected AMs from the tumor periphery and distant segments in 13 resected lungs by bronchoalveolar lavage (BAL) procedure and compared mRNA expression. AMs in the tumor periphery expressed significantly higher levels of IL-10 and CCL2 than those in the distant segment (p < 0.01 and p = 0.03, respectively). Additionally, IL-10 and CCL2 significantly induced the growth and migration of the PC9 cells in vitro. This study suggests that p-exAMs should be considered as a tumor-promoting component in the tumor microenvironment.