title: The role of CCL20/CCR6 axis in recruiting Treg cells to tumor sites of NSCLC patients.
abstract: Inflammatory chemokine CCL20 and its receptor CCR6 have been reported to correlate with colorectal cancer patients' metastasis. However, the role of CCL20 in patients with NSCLC is not well defined. In this study, we detected the expression of CCL20 in tumor samples and corresponding adjacent ones (n=71) from patients with NSCLC using RT-PCR and observed that CCL20 showed higher expression in tumor samples (0.28±0.17) than in adjacent ones (0.20±0.13) (n=71, P=0.0056), which was also verified in protein level using IHC. Analysis results showed that CCL20 expression was positively associated with CD4 (n=80, P=0.0046), Foxp3 (n=80, P=0.0020) and IL-10 (n=61, P=0.0003) in tumor samples. And the flow data showed that Treg cells accumulated in TIL (MFI: 961±760) compared with PBMC (MFI: 683±460) (n=40, P=0.0046); and the percentage of CCR6 - the sole receptor of CCL20 - on Treg cells was higher in TIL (MFI: 1311±1268) than in PBMC (MFI: 976±780) (n=40, P=0.0219). It was interesting to find that the expression of CCL20 in tumor sites was almost 1.5-fold higher in samples from high-stage patients (III-IV stage, 0.34±0.17) compared with those from low-stage patients (I-II stage, 0.22±0.11) (P=0.0056). Furthermore, the higher expression of CCL20 was associated with a lower overall survival (P=0.0198). The IHC data showed that tumor cells were the main source of CCL20, and after treated cell line A549 with docetaxel, we found that the secretion of CCL20 was decreased heavily (n=3, P=0.0046). Our results demonstrated that CCL20 cooperated with CCR6 could recruit Treg cells to tumor sites, and chemotherapy medicine docetaxel could decrease the expression of CCL20.
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Key Laboratory of Thoracic Tumors of Zhengzhou, Zhengzhou 450052, Henan, China.
authors: Chun-Yang
authors: CY
authors: Zhang
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Yu
authors: Y
authors: Qi
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Xiang-Nan
authors: XN
authors: Li
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Dong-Lei
authors: DL
authors: Liu
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Jia
authors: J
authors: Zhao
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Deng-Yan
authors: DY
authors: Zhu
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Kai
authors: K
authors: Wu
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Xu-Dong
authors: XD
authors: Zhou
authors: Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: zhaosong@zzu.edu.cn.
authors: Song
authors: S
authors: Zhao
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D043823:Taxoids / Q000494:pharmacology
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6; D043823:Taxoids; D000077143:Docetaxel
keywords: CCL20; Docetaxel; NSCLC