The activating receptor NKG2D (natural-killer group 2, member D) and its ligands play an important role in the NK, γδ+ and CD8+ T-cell-mediated immune response to tumors. Ligands for NKG2D are rarely detectable on the surface of healthy cells and tissues, but are frequently expressed by tumor cell lines and in tumor tissues. It is evident that the expression levels of these ligands on target cells have to be tightly regulated to allow immune cell activation against tumors, but at the same time avoid destruction of healthy tissues. Many tumor cell lines and primary tumors from diverse tissue origins express NKG2D ligands. Ovarian carcinoma cells express low amounts of the NKG2D ligands MICA, ULBP1, and ULBP3, whereas ULBP2 was more highly expressed. NKG2D ligands were highly expressed in lymph node metastasis of stage I colorectal cancer samples, but they were expressed in lower amounts in Stage II, III, or IV tumors.
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