CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells

被引：56

作者：

Chen, Zhangguo ^{[1
]}

Chen, Lanfen ^{[1
]}

Baker, Kristi ^{[1
]}

Olszak, Torsten ^{[1
]}

Zeissig, Sebastian ^{[1
]}

Huang, Yu-Hwa ^{[1
]}

Kuo, Timothy T. ^{[1
]}

Mandelboim, Ofer ^{[2
]}

Beauchemin, Nicole ^{[3
,4
,5
,6
]}

Lanier, Lewis L. ^{[7
,8
]}

Blumberg, Richard S. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Med, Gastroenterol Div,Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel

[3] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada

[4] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[5] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada

[6] McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada

[7] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2011年 / 208卷 / 13期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

INTRACELLULAR RETENTION; ELEVATED EXPRESSION; GENE; PROGRESSION; ACTIVATION; MECHANISM; MELANOMA; RECEPTOR; CD66A;

D O I：

10.1084/jem.20102575

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Although carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) has been viewed as a tumor suppressor, increasing clinical evidence shows that high levels of CEACAM1 expression on tumors correlates with poor prognosis and high risk of metastasis. Here, we examined the consequences of CEACAM1 expression on tumor cells. We show that tumor cell-associated CEACAM1 causes intracellular retention of various NKG2D ligands in mouse and human tumor cells. CEACAM1-silenced tumor cells expressed more cell surface NKG2D ligands and exhibited greater sensitivity to natural killer cell-mediated cytolysis in vitro and rejection in vivo. Our studies reveal a novel mechanism through which CEACAM1-bearing tumor cells may escape immune-surveillance.

引用

页码：2633 / 2640

页数：8

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