The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the ceff-surface receptor CRTAM

被引:144
作者
Boles, KS
Barchet, W
Diacovo, T
Cella, M
Colonna, M
机构
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
关键词
D O I
10.1182/blood-2005-02-0817
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The tumor suppressor in lung cancer-1 (TSLC1) gene is frequently silenced in human lung carcinomas, and its expression suppresses tumorigenesis in nude mice. TSLC1 encodes a cell-surface protein called Necl-2 that belongs to the Nectin and Nectin-like (Necl) family of molecules. Necl-2 mediates epithelial cell junctions by homotypic contacts and/or heterotypic interactions with other Nec-tins and Necls. Thus, it inhibits tumorigenesis by ensuring that epithelial cells grow in organized layers. Here, we demonstrate that natural killer (NK) cells and CD8(+) T cells recognize Necl-2 through a receptor known as class I-restricted T-cell-associated molecule (CRTAM), which is expressed only on activated cells. CRTAM-Necl-2 interactions promote cytotoxicity of NK cells and interferon gamma (IFN-gamma) secretion of CD8(+) T cells in vitro as well as NK cell-mediated rejection of tumors expressing Necl-2 in vivo. These results provide evidence for an additional mechanism of tumor suppression mediated by TSLC1 that involves cytotoxic lymphocytes. Furthermore, they reveal Necl-2 as one of the molecular targets that allows the immunosurveillance network to distinguish tumor cells from normal cells.
引用
收藏
页码:779 / 786
页数:8
相关论文
共 66 条
[61]   Tumor-specific shared antigenic peptides recognized by human T cells [J].
van der Bruggen, P ;
Zhang, Y ;
Chaux, P ;
Stroobant, V ;
Panichelli, C ;
Schultz, ES ;
Chapiro, J ;
Van den Eynde, BTJ ;
Brasseur, F ;
Boon, T .
IMMUNOLOGICAL REVIEWS, 2002, 188 :51-64
[62]   Expression and functional characterization of the adhesion molecule spermatogenic immunoglobulin superfamily in the mouse testis [J].
Wakayama, T ;
Koami, H ;
Ariga, H ;
Kobayashi, D ;
Sai, Y ;
Tsuji, A ;
Yamamoto, M ;
Iseki, S .
BIOLOGY OF REPRODUCTION, 2003, 68 (05) :1755-1763
[63]   Cloning and characterization of a novel mouse immunoglobulin superfamily gene expressed in early spermatogenic cells [J].
Wakayama, T ;
Ohashi, K ;
Mizuno, K ;
Iseki, S .
MOLECULAR REPRODUCTION AND DEVELOPMENT, 2001, 60 (02) :158-164
[64]  
WANG PL, 1992, J IMMUNOL, V148, P2600
[65]  
Yageta M, 2002, CANCER RES, V62, P5129
[66]   A greedy algorithm for aligning DNA sequences [J].
Zhang, Z ;
Schwartz, S ;
Wagner, L ;
Miller, W .
JOURNAL OF COMPUTATIONAL BIOLOGY, 2000, 7 (1-2) :203-214