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

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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

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Neoplasms
Ligands
Natural Killer Cells
NK Cell Lectin-Like Receptor Subfamily K
Immunologic Monitoring
Prostatic Neoplasms
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Guerra, N., Tan, Y. X., Joncker, N. T., Choy, A., Gallardo, F., Xiong, N., ... 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
Guerra, Nadia ; Tan, Ying Xim ; Joncker, Nathalie T. ; Choy, Augustine ; Gallardo, Fermin ; Xiong, Na ; Knoblaugh, Susan ; Cado, Dragana ; Greenberg, Norman R. ; Raulet, David H. / NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy. In: Immunity. 2008 ; Vol. 28, No. 4. pp. 571-580.
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Guerra, N, Tan, YX, Joncker, NT, Choy, A, Gallardo, F, Xiong, N, Knoblaugh, S, Cado, D, Greenberg, NR & Raulet, DH 2008, 'NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy', Immunity, vol. 28, no. 4, pp. 571-580. https://doi.org/10.1016/j.immuni.2008.02.016

NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy. / Guerra, Nadia; Tan, Ying Xim; Joncker, Nathalie T.; Choy, Augustine; Gallardo, Fermin; Xiong, Na; Knoblaugh, Susan; Cado, Dragana; Greenberg, Norman R.; Raulet, David H.

In: Immunity, Vol. 28, No. 4, 11.04.2008, p. 571-580.

Research output: Contribution to journalArticle

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Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F, Xiong N et al. NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy. Immunity. 2008 Apr 11;28(4):571-580. https://doi.org/10.1016/j.immuni.2008.02.016