TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer.
BACKGROUND
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.


OBJECTIVE
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.


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-alpha, IL-1beta) 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.
Ho
Chao-Chi
CC
Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan 100, Republic of China. pcyang@ntu.edu.tw
Liao
Wei-Yu
WY
Wang
Cheng-Yi
CY
Lu
Yin-Hsiu
YH
Huang
Hsin-Yi
HY
Chen
Hsuan-Yu
HY
Chan
Wing-Kai
WK
Chen
Huei-Wen
HW
Yang
Pan-Chyr
PC
D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D010996:Pleural Effusion / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1