NKG2D function protects the host from tumor initiation

被引:254
作者
Smyth, MJ [1 ]
Swann, J
Cretney, E
Zerafa, N
Yokoyama, WM
Hayakawa, Y
机构
[1] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic 3002, Australia
[2] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
关键词
D O I
10.1084/jem.20050994
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The activation NKG2D receptor has been shown to play an important role in the control of experimental tumor growth and metastases expressing ligands for NKG2D; however, a function for this recognition pathway in host protection from de novo tumorigenesis has never been demonstrated. We show that neutralization of NK62D enhances the sensitivity of wild-type (WT) C57BL/6 and BALB/c mice to methylcholanthrene (MCA)-induced fibrosarcoma. The importance of the NK62D pathway was additionally illustrated in mice deficient for either IFN-gamma or tumor necrosis factor-related apoptosis-inducing ligand, whereas mice depleted of natural killer cells, T cells, or deficient for perforin did not display any detectable NKG2D phenotype. Furthermore, IL-12 therapy preventing MCA-induced sarcoma formation was also largely dependent on the NK62D pathway. Although NK62D ligand expression was variable or absent on sarcomas emerging in WT mice, sarcomas derived from perforin-deficient mice were Rae-1(+) and immunogenic when transferred into WT syngeneic mice. These findings suggest an important early role for the NKG2D in controlling and shaping tumor formation.
引用
收藏
页码:583 / 588
页数:6
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