Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO
Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO
复制标题
肝细胞癌相关成纤维细胞通过 PGE2 和 IDO 触发 NK 细胞功能障碍
DOI：
10.1016/j.canlet.2011.12.020
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发表时间：
2012-05-28
期刊：
影响因子：
9.7
通讯作者：
Chen, Guihua
中科院分区：
文献类型：
--
作者：
Li, Tuanjie;Yang, Yang;Chen, Guihua
自然杀伤(NK)细胞功能缺陷是肿瘤免疫逃逸所必需的，但人类癌症的潜在调控机制在很大程度上仍不清楚。我们发现，肝细胞癌成纤维细胞在诱导NK细胞功能障碍方面明显优于包皮成纤维细胞，其特点是细胞毒分子和细胞表面标志的低表达，细胞因子的产生减少，体外对K562细胞的杀伤作用降低。我们的结果还表明，来自激活的成纤维细胞的PGE2和IDO可以抑制NK细胞的激活，从而为肿瘤的进展创造有利的条件。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
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.