Overexpression of natural killer group 2 member D ligands predicts favorable prognosis in cholangiocarcinoma

被引：36

作者：

Tsukagoshi, Mariko ^{[1
]}

Wada, Satoshi ^{[1
,2
]}

Yokobori, Takehiko ^{[3
]}

Altan, Bolag ^{[1
]}

Ishii, Norihiro ^{[1
]}

Watanabe, Akira ^{[1
]}

Kubo, Norio ^{[1
]}

Saito, Fumiyoshi ^{[1
]}

Araki, Kenichiro ^{[1
]}

Suzuki, Hideki ^{[1
]}

Hosouchi, Yasuo ^{[4
]}

Kuwano, Hiroyuki ^{[1
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

[2] Kanagawa Canc Ctr, Dept Canc Immunotherapy, 1-1-2 Nakao, Yokohama, Kanagawa 2410815, Japan

[3] Gunma Univ, Grad Sch Med, Dept Mol Pharmacol & Oncol, Maebashi, Gunma 371, Japan

[4] Gunma Prefecture Saiseikai Maebashi Hosp, Dept Surg & Laparoscop Surg, Maebashi, Gunma, Japan

来源：

CANCER SCIENCE | 2016年 / 107卷 / 02期

基金：

日本学术振兴会;

关键词：

Cholangiocarcinoma; immunohistochemistry; MHC class I chain-related proteins A and B; natural killer group 2 member D; unique long 16 binding protein; NKG2D LIGANDS; PD-1; BLOCKADE; T-CELLS; EXPRESSION; RECEPTOR; MICA; CYTOTOXICITY; INDICATOR; TRENDS; ULBP2;

D O I：

10.1111/cas.12853

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The natural killer group 2 member D (NKG2D) receptor and its ligands are important mediators of immune responses to tumors. NKG2D ligands are overexpressed in several malignant tumor types; however, the prognostic value of these ligands is unclear. Here, we aimed to elucidate the role of NKG2D ligands in extrahepatic cholangiocarcinoma (EHCC). We therefore investigated the expression of the NKG2D receptor and its ligands MHC class I chain-related proteins A and B (MICA/B), unique long 16 binding protein (ULBP) 1, and ULBP2/5/6 in resected specimens from 82 patients with EHCC. All NKG2D ligands were highly expressed in EHCC. High expression of MICA/B or ULBP2/5/6 correlated with overall and disease-free survival. In contrast, high expression of ULBP1 was significantly associated with improved overall survival, but not disease-free survival. Concurrent high expression of multiple NKG2D ligands revealed significantly better overall and disease-free survival than that observed with the overexpression of any one NKG2D ligand. Co-expression of multiple NKG2D ligands was an independent prognostic indicator of improved survival. Furthermore, co-overexpression of multiple NKG2D ligands was significantly correlated with high expression of the NKG2D receptor. Inhibiting interactions between multiple NKG2D ligands and the NKG2D receptor might be a promising approach for controlling cancer progression and improving patient prognosis in EHCC.

引用

页码：116 / 122

页数：7

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