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

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

doi:10.18632/oncotarget.9639

Guangbo Zhang, Haitao Huang + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.9639

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Journal: Oncotarget	Publication Date: May 26, 2016
Citations: 8	License type: cc-by

Affiliation: First Affiliated Hospital of Soochow University

Abstract

ObjectiveTo explore the expression feature and biological functions of TREM-1 on tumor-associated macrophages (TAMs) in lung cancer.ResultsThe 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.MethodsA 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.ConclusionThe 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.

Highlights

tumor-associated macrophages (TAMs) are major component of leukocytic infiltrate of tumors and play a pivotal role for tumorigenesis, invasion and metastasis in various solid tumors [1,2]
The low expression level of triggering receptor expressed on myeloid cells-1 (TREM-1) might be a characteristic for TAMs in lung cancer
In non-small cell lung cancer (NSCLC) patients and tumorbearing mouse model, our results demonstrated that the expression levels of TREM-1 on monocytes/macrophages were significantly decreased during tumor progression

Summary

Introduction

TAMs are major component of leukocytic infiltrate of tumors and play a pivotal role for tumorigenesis, invasion and metastasis in various solid tumors [1,2]. M1 type macrophages refer to the “classicallyactivated” macrophage that emerge during cell-mediated immune responses and play anti-tumor roles, whereas M2 type macrophages are the majority of TAMs, which have anti-inflammatory and pro-tumoral properties [3,4,5]. Their dynamic balance is essential for tumor development [4,5]. Www.impactjournals.com/oncotarget identification for the phenotype of monocytes/macrophages in tumor condition would be important to understand their roles in tumor progression

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