NKG2D-deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy

Immunity. 2008 Apr;28(4):571-80. doi: 10.1016/j.immuni.2008.02.016.

Abstract

Ligands for the NKG2D stimulatory receptor are frequently upregulated on tumor lines, rendering them sensitive to natural killer (NK) cells, but the role of NKG2D in tumor surveillance has not been addressed in spontaneous cancer models. Here, we provided the first characterization of NKG2D-deficient mice, including evidence that NKG2D was not necessary for NK cell development but was critical for immunosurveillance of epithelial and lymphoid malignancies in two transgenic models of de novo tumorigenesis. In both models, we detected NKG2D ligands on the tumor cell surface ex vivo, providing needed evidence for ligand expression by primary tumors. In a prostate cancer model, aggressive tumors arising in NKG2D-deficient mice expressed higher amounts of NKG2D ligands than did similar tumors in wild-type mice, suggesting an NKG2D-dependent immunoediting of tumors in this model. These findings provide important genetic evidence for surveillance of primary tumors by an NK receptor.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Animals
  • Benz(a)Anthracenes / toxicity
  • Disease Models, Animal
  • Female
  • Fibrosarcoma / chemically induced
  • Fibrosarcoma / genetics
  • Fibrosarcoma / immunology*
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Surveillance* / genetics
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Male
  • Methylcholanthrene
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily K
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology*
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / physiology
  • Receptors, Natural Killer Cell

Substances

  • Benz(a)Anthracenes
  • Klrk1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Methylcholanthrene