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436 Advances in Cancer Therapy

receptors and their ligands (Fig. 1), so that the NK cell-mediated immunotherapy can be carried out fully to cure malignancies. So the regulation expression of NK cell receptors and their ligands provides a strategy for targeting gene expression in tumor cells, and may be with minimal offtarget consequences (Villar-Garea and Esteller, 2004; Bhalla, 2005; Szyf,

Fig. 1. Transcription regulation and epigenetic control of KIR and NKG2 receptors and their ligands. A dendrogram representing the relatedness of different KIR and NKG2 receptors (blue) and their ligands (green) to each other, and the extent of the sequence relatedness between two genes is shown by the distance of the lines (Raulet, 2003). The left oval shows the gene regulation in transcription factor level, while the right oval shows the gene regulation in epigenetic level, and the overlapping part shows the co-regulation.

NK cells not only are important players of innate effecter responses, but also participate in the initiation and development of antigen-specific responses through secretion of immunoregulatory cytokines (such as IFN-, tumor necrosis factor- (TNF-) and granulocyte–macrophage colony-stimulating factor (GM–CSF)) and through cell-to-cell contact (Biron et al., 1999). Regulation of the expression of NK-cell receptors and their ligands refers to the control of the amount, the timing of appearance, and the functional products of these genes, leading to the flexibility of NK cells or other immune cells to adapt to a variable environment, external signals, and damages to target cells (Wu et al., 2005). In particular, the modification of NK-cell receptors and their ligands is a potential therapeutic implication for cancer treatment. Although the regulation mechanism of expression of NKcell receptors and related ligands has acquired important progress at the transcription level, the regulatory mechanisms of a number of crucial receptors and ligands, for example signaling lymphocytic activating molecule (SLAM)-related receptors (CD150, 2B4, Ly-9,

2005, Stein et al., 2010).

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**Part 5** 

**Cancer Diagnostic Technologies** 

