Oncotarget

Research Papers:

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

Guangbo Zhang _, Hongmei Liu, Jian Huang, Siwen Chen, Xudong Pan, Haitao Huang and Ling Wang

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Oncotarget. 2016; 7:40508-40517. https://doi.org/10.18632/oncotarget.9639

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Abstract

Guangbo Zhang1,*, Hongmei Liu2,*, Jian Huang3, Siwen Chen2, Xudong Pan2, Haitao Huang4, Ling Wang1,2

1Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China

2Department of Special Procurement Ward, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China

3Department of Emergency, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China

4Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215007, China

*These authors have contributed equally to this work

Correspondence to:

Ling Wang, email: wangling40@126.com

Guangbo Zhang, email: 15962254210@163.com

Keywords: TREM-1, tumor-associated macrophages, tumor microenvironment, lung cancer

Received: September 14, 2015    Accepted: April 25, 2016    Published: May 26, 2016

ABSTRACT

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.


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