TREM-1 Is Induced in Tumor Associated Macrophages by Cyclo-Oxygenase Pathway in Human Non-Small Cell Lung Cancer

Abstract

It is increasingly recognized that the tumor microenvironment plays a critical role in the initiation and progression of lung cancer. In particular interaction of cancer cells, macrophages, and inflammatory response in the tumor microenvironment has been shown to facilitate cancer cell invasion and metastasis. The specific molecular pathways in macrophages that immunoedit tumor growth are not well defined. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a member of the super immunoglobulin family expressed on a select group of myeloid cells mainly monocyte/macrophages. Recent studies suggest that expression of TREM-1 in tumors may predict cancer aggressiveness and disease outcomes in liver and lung cancer however the mechanism of TREM-1 expression in the setting of cancer is not defined. In this study we demonstrate that tumor tissue from patients with non-small cell lung cancer show an increased expression of TREM-1 and PGE2. Immunohistochemistry and immunofluorescence confirmed that the expression of TREM-1 was selectively seen in CD68 positive macrophages. By employing an in vitro model we confirmed that expression of TREM-1 is increased in macrophages that are co-cultured with human lung cancer cells. Studies with COX-2 inhibitors and siCOX-2 showed that expression of TREM-1 in macrophages in tumor microenvironment is dependent on COX-2 signaling. These studies for the first time define a link between tumor COX-2 induction, PGE2 production and expression of TREM-1 in macrophages in tumor microenvironment and suggest that TREM-1 might be a novel target for tumor immunomodulation.

Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance

“…Previous studies have shown the ability of cancer cells to polarize macrophages, utilizing cytokine analysis, immunohistochemistry, and gene amplification to characterize the effects of coculturing macrophages with cancer cells. 39–41 In a study by Muller-Quernheim et al , both the coculture of tumor cells with macrophages and the treatment of macrophages with media taken from tumor cell cultures resulted in an increased activity for both M1 and M2-like macrophages, with a slight skewing toward a M2-like phenotype. 42 Furthermore, this study used A549 cells, the same line investigated in the work presented here.…”

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

“…[32][33][34] All rats were sacriced by luxation of cervical vertebra to collect the same section of the right lung tissue, which was then xed in 10% neutral formalin and embedded in paraffin. Paraffin sections were deparaffinized, rehydrated in xylene and ethanol and then treated with 3% H 2 O 2 (Boster Biological Technology, Ltd, Wuhan, CN) for 10 min to suppress endogenous peroxidase activity and reduce background staining.…”

Diagnostic value of TREM-1 and TREM-2 expression in bronchoalveolar lavage fluid in sarcoidosis and other lung diseases

“…There are only a few studies analysing TREM receptors expression in lung cancer. Yuan found an increased expression of TREM-1 in tumour tissues from patients with non-small cell lung cancer (28). No studies investigating TREM-2 receptor in lung cancer have been published yet.…”