TREM-1(low) is a novel characteristic for tumor-associated macrophages in lung cancer

OBJECTIVE: To explore the expression feature and biological functions of TREM-1 on tumor-associated macrophages (TAMs) in lung cancer. RESULTS: The levels of TREM-1 on tissue-infiltrating monocytes/macrophage from tumor nest were significantly lower than those from nonturmor tissue or peripheral blood samples. Clinical analysis indicated that the levels of TREM-1-related TAMs were significantly decreased during cancer stages progression. The tumor-bearing mouse model further confirmed that the expression of TREM-1 on TAMs was significantly decreased with tumor growth. In addition, we found the activation of TREM-1 could significantly enhance the secretion of IL-1β by TAM in vitro. Furthermore, T-bet but not Eomes was found to be the key transcription factor for the TREM-1 expression on monocytes/macrophage. METHODS: A total of 40 patients with non-small cell lung cancer (NSCLC) were enrolled in this study. The expression characteristics of TREM-1 in blood and tissue-infiltrating monocytes/macrophage were examined by flow cytometry analysis. After the treatment of TREM-1 antibody, which is an agonist of TREM-1, cytokines secreted by TAM were then analyzed. In LLC-tumor bearing mouse model, we further investigated the dynamic expression feature of TREM-1 on macrophage with tumor growth. Moreover, we explored the transcription factor for regulating TREM-1 expression on monocyes/macrophage with wildtype, T-bet Ko or Eomes Ko mice. CONCLUSION: The levels of TREM-1 were remarkably decreased during tumor progression. The low expression level of TREM-1 might be a characteristic for TAMs in lung cancer.