Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.00456
Keywords
toll-like receptor 4; non-small cell lung cancer; programmed cell death ligand 1; soluble toll-like receptor 4; tumor microenvironment
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Funding
- National Natural Science Foundation of China [81672697]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2015ZX09102018]
- Scientific Research Cultivation Fund of Tianjin Society of Anesthesiology [TJMZJJ-2016-01]
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Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4) levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041), increased clinical TNM stage (P < 0.001), and presence of lymphatic invasion (P < 0.001). Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = -0.485, P = 0.003). TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001). Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.
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