原创力文档selective recruitment of regulatory t cell through ccr6-ccl20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis选择招聘的调节性t细胞在肝细胞癌ccr6-ccl20促进肿瘤进展和预测预后不良.pdfVIP
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selective recruitment of regulatory t cell through ccr6-ccl20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis选择招聘的调节性t细胞在肝细胞癌ccr6-ccl20促进肿瘤进展和预测预后不良
Selective Recruitment of Regulatory T Cell through
CCR6-CCL20 in Hepatocellular Carcinoma Fosters Tumor
Progression and Predicts Poor Prognosis
1 1,2 1 1 1 1
Kang-Jie Chen , Sheng-Zhang Lin , Lin Zhou , Hai-Yang Xie , Wu-Hua Zhou , Ahmed Taki-Eldin ,
Shu-Sen Zheng1*
1 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,
2 Department of General Surgery, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
Abstract
Background: Regulatory T cells (Tregs) are highly prevalent in tumor tissue and can suppress effective anti-tumor immune
responses. However, the source of the increased tumor-infiltrating Tregs and their contribution to cancer progression
remain poorly understood.
Methodology/Principal Finding: We here investigated the frequency, phenotype and trafficking property of Tregs and their
prognostic value in patients with hepatocellular carcinoma (HCC). Our results showed that FoxP3+ Tregs highly aggregated
and were in an activated phenotype (CD69+ HLA-DRhigh) in the tumor site, where they can suppress the proliferation and
INF-c secretion of CD4+CD252 T cells. These tumor-infiltrating Tregs could be selectively recruited though CCR6-CCL20 axis
as illustrated by (a) high expression of CCR6 on circulating Tregs and their selective migration to CCR6 ligand CCL20, and (b)
correlation of distribution and expression between tumor-infiltrating Tregs and intratumoral CCL20. In addition, we found
that the number of tumor-infiltrating Tregs was associated with cirrhosis background (P = 0.011) and tumor differentiation
(P = 0.003), and was an independent prognostic factor for overall surviv
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