title: 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.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhangguo
authors.initials: Z
authors.lastname: Chen
authors.forename: Lanfen
authors.initials: L
authors.lastname: Chen
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.forename: Torsten
authors.initials: T
authors.lastname: Olszak
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zeissig
authors.forename: Yu-Hwa
authors.initials: YH
authors.lastname: Huang
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Kuo
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K