TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer
Journal
American Journal of Respiratory and Critical Care Medicine
Journal Volume
177
Journal Issue
7
Pages
763-770
Date Issued
2008
Author(s)
Wang C.-Y.
Lu Y.-H.
Huang H.-Y.
Chen H.-Y.
Chan W.-K.
Abstract
Rationale: Triggering receptor expressed on myeloid cells (TREM)-1 is a molecule crucial for the triggering and amplification of inflammatory response and a new biomarker for sepsis. Tumor-associated macrophages and inflammation in the tumor microenvironment are also involved in cancer progression. Objectives: To determine the role of TREM-1 in tumor-associated macrophage and cancer progression. Methods: Using ELISA and Western blot, we measured soluble TREM-1 levels in 65 pleural effusions of various etiologies. We evaluated TREM-1-positive cells by immunocytochemistry in malignant pleural effusion and in lung tumor versus adjacent normal tissue in surgical specimens from 68 patients with non-small cell lung cancer (NSCLC). TREM-1 expression was correlated with patient survival. TREM-1 expression in primary isolated peripheral blood macrophages cocultured with lung cancer cell lines was determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Measurements and Main Results: Soluble TREM-1 and tumor-associated macrophage TREM-1 expression was increased in malignant pleural effusions in patients with NSCLC. Lung cancer cells could directly up-regulate TREM-1 and proinflammatory cytokine (tumor necrosis factor-α, IL-1β) expression in primary isolated peripheral blood macrophages in coculture experiments. Increased TREM-1-positive tumor-associated macrophages in tumor tissue of patients with NSCLC were associated with reduced disease-free (P = 0.011) and overall survival (P = 0.004). Multivariate Cox regression analysis indicated that TREM-1 was an independent predictor of patient survival (hazard ratio, 2.72; 95% confidence interval, 1.33-5.57; P = 0.006). Conclusions: Cancer cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1 expression in tumor-associated macrophages is associated with cancer recurrence and poor survival of patients with NSCLC. TREM-1 and the inflammatory response may play an important role in cancer progression.
SDGs
Other Subjects
interleukin 1beta; triggering receptor expressed on myeloid cells 1; tumor necrosis factor alpha; immunoglobulin receptor; membrane protein; TREM1 protein, human; unclassified drug; adult; aged; article; cancer cell culture; cancer growth; cancer survival; cell culture; controlled study; enzyme linked immunosorbent assay; female; human; human cell; human tissue; lung non small cell cancer; major clinical study; male; outcome assessment; pleura effusion; priority journal; protein expression; reverse transcription polymerase chain reaction; tumor associated leukocyte; Western blotting; disease course; immunology; inflammation; Kaplan Meier method; lung tumor; macrophage; metabolism; middle aged; multivariate analysis; pathology; prognosis; proportional hazards model; prospective study; upregulation; Carcinoma, Non-Small-Cell Lung; Disease Progression; Female; Humans; Inflammation; Kaplan-Meiers Estimate; Lung Neoplasms; Macrophages; Male; Membrane Glycoproteins; Middle Aged; Multivariate Analysis; Pleural Effusion; Prognosis; Proportional Hazards Models; Prospective Studies; Receptors, Immunologic; Up-Regulation
Type
journal article