NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy
NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy
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DOI：
10.1016/j.immuni.2008.02.016
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发表时间：
2008-04-01
期刊：
影响因子：
32.4
通讯作者：
Raulet, David H.
中科院分区：
文献类型：
--
作者：
Guerra, Nadia;Tan, Ying Xim;Raulet, David H.
NKG2D刺激受体的配体在肿瘤细胞系中经常上调，使其对自然杀伤（NK）细胞敏感，但NKG2D在肿瘤监测中的作用尚未在自发性癌症模型中得到解决。在这里，我们提供了NKG2D缺陷小鼠的第一个特征，包括NKG2D不是NK细胞发育所必需的证据，但在两种从头肿瘤发生的转基因模型中，NKG2D对上皮和淋巴恶性肿瘤的免疫监视至关重要。在这两种模型中，我们在离体肿瘤细胞表面检测到NKG2D配体，为原发性肿瘤的配体表达提供了所需的证据。在前列腺癌模型中，NKG2D缺陷小鼠中出现的侵袭性肿瘤表达的NKG2D配体量高于野生型小鼠中的类似肿瘤，表明该模型中肿瘤的NKG2D依赖性免疫编辑。这些发现为NK受体监测原发性肿瘤提供了重要的遗传学证据。
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.