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

J Exp Med. 2011 Dec 19;208(13):2633-40. doi: 10.1084/jem.20102575. Epub 2011 Dec 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immunity, Cellular
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Ligands
  • Mice
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily K / agonists*
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • Neoplasm Metastasis
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Tumor Escape / immunology*


  • 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