NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy.
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.
Guerra
Nadia
N
Department of Molecular and Cell Biology, 489 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720, USA.
Tan
Ying Xim
YX
Joncker
Nathalie T
NT
Choy
Augustine
A
Gallardo
Fermin
F
Xiong
Na
N
Knoblaugh
Susan
S
Cado
Dragana
D
Greenberg
Norman M
NM
Greenberg
Norman R
NR
Raulet
David H
DH
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D007157:Immunologic Surveillance / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D055607:Receptors, Natural Killer Cell
D001551:Benz(a)Anthracenes; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D008748:Methylcholanthrene