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NKG2D ligands in tumor immunity

Oncogene volume 27, pages 5944–5958 (2008)Cite this article

Abstract

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. Importantly, it was recently discovered that another safeguard mechanism controlling activation via the receptor NKG2D exists. It was shown that NKG2D signaling is coupled to the IL-15 receptor pathway in a cell-specific manner suggesting that priming of NKG2D-mediated activation depends on the cellular microenvironment and the distinct cellular context. This review will provide a broad overview of our up-to-date knowledge of the NKG2D receptor and its ligands in the context of tumor immunology. Strategies to amplify NKG2D-mediated antitumor responses and counteract tumor immune escape mechanisms will be discussed.

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Acknowledgements

We thank Professor Lewis Lanier and Ioanna Galani for critically reading the paper. The work is supported by a Marie Curie Excellent Grant, Deutsche José Carreras Leukämie Stiftung, German-Israel DKFZ/MOST cooperation and Boehringer Ingelheim Fonds. We want to apologize to all authors whose work could not be cited in this review because of space limitations.

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  1. Division of Innate Immunity, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany

    N Nausch & A Cerwenka

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Nausch, N., Cerwenka, A. NKG2D ligands in tumor immunity. Oncogene 27, 5944–5958 (2008). https://doi.org/10.1038/onc.2008.272

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