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Blood, 1 August 2005, Vol. 106, No. 3, pp. 779-786.
Prepublished online as a Blood First Edition Paper on April 5, 2005; DOI 10.1182/blood-2005-02-0817.


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PLENARY PAPERS

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

Kent S. Boles, Winfried Barchet, Tom Diacovo, Marina Cella, and Marco Colonna

From the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO; and the Department of Pediatrics, Washington University School of Medicine, St Louis, MO.

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 Nectins 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.


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