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

Abstract	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.
Authors	Zhangguo Chen, Lanfen Chen, Kristi Baker, Torsten Olszak, Sebastian Zeissig, Yu-Hwa Huang, Timothy T Kuo, Ofer Mandelboim, Nicole Beauchemin, Lewis L Lanier, Richard S Blumberg
Journal	The Journal of experimental medicine (J Exp Med) Vol. 208 Issue 13 Pg. 2633-40 (Dec 19 2011) ISSN: 1540-9538 [Electronic] United States
PMID	22143889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, CD CD66 antigens Carcinoembryonic Antigen Ceacam1 protein, mouse Cell Adhesion Molecules KLRK1 protein, human Klrk1 protein, mouse Ligands NK Cell Lectin-Like Receptor Subfamily K
Topics	Animals Antigens, CD (genetics, immunology) Carcinoembryonic Antigen (genetics, immunology) Cell Adhesion Molecules (genetics, immunology) Cell Line, Tumor Gene Expression Regulation, Neoplastic (immunology) Humans Immunity, Cellular Killer Cells, Natural (immunology, pathology) Ligands Mice Mice, Knockout NK Cell Lectin-Like Receptor Subfamily K (agonists, genetics, immunology) Neoplasm Metastasis Neoplasms (immunology, pathology) Tumor Escape (immunology)

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