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Tumor cell recognition by the NK cell activating receptor NKG2D

Evidence for increased tumor incidence in NKG2D‐deficient mice has set NKG2D as the first innate immune receptor implicated in immunosurveillance of tumors. In this viewpoint article, we discuss recent genetic insight into NKG2D‐mediated suppression of spontaneous tumor development in the context of NKG2D signaling properties. Moreover, we identify unresolved issues and consider how an understanding of NKG2D‐receptor and ‐ligand biology can facilitate successful therapeutic intervention of human cancer.