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

Nadia Guerra, Ying Xim Tan, Nathalie T. Joncker, Augustine Choy, Fermin Gallardo, Na Xiong, Susan Knoblaugh, Dragana Cado, Norman R. Greenberg, David H. Raulet

Research output: Contribution to journalArticle

484 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalImmunity
Volume28
Issue number4
DOIs
StatePublished - Apr 11 2008
Externally publishedYes

Keywords

  • CELLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Guerra, N., Tan, Y. X., Joncker, N. T., Choy, A., Gallardo, F., Xiong, N., Knoblaugh, S., Cado, D., Greenberg, N. R., & Raulet, D. H. (2008). NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy. Immunity, 28(4), 571-580. https://doi.org/10.1016/j.immuni.2008.02.016