Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO

被引：260
作者：
Li, Tuanjie [1 ,2 ]
Yang, Yang [2 ]
Hua, Xuefeng [1 ,2 ]
Wang, Guoying [2 ]
Liu, Wei [1 ]
Jia, Changchang [2 ]
Tai, Yan [1 ,2 ]
Zhang, Qi [1 ,3 ]
Chen, Guihua [1 ,2 ]
机构：
[1] Guangdong Prov Key Lab Liver Dis Res, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Hepat Surg, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 3, Cellgene Therapy Translat Med Res Ctr, Guangzhou 510275, Guangdong, Peoples R China
来源：
CANCER LETTERS | 2012年 / 318卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Hepatocellular carcinoma; Cancer-associated fibroblasts; Natural killer cells; Prostaglandin E2; Indoleamine 2,3-dioxygenase; DENDRITIC CELLS; HUMAN BREAST; GRANZYME-B; STROMA; DIFFERENTIATION; PROGRESSION; ACTIVATION; MODULATE; TARGET; TUMORS;
D O I：
10.1016/j.canlet.2011.12.020
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Defects in natural killer (NK) cell function are necessary for tumor immune escape, but the underlying regulatory mechanisms in human cancers remain largely unknown. Here we show that fibroblasts derived from hepatocellular carcinoma (HCC) were significantly superior to foreskin-derived fibroblasts at inducing NK cell dysfunction, which is characterized by low expression of cytotoxic molecules and surface markers for cell activation, impaired production of cytokines, and decreased cytotoxicity against K562 cells in vitro. Our results also indicate that PGE2 and IDO, derived from activated fibroblasts, suppress the activation of NK cells and thereby create favorable conditions for tumor progression. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：154 / 161
页数：8
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