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Oncoimmunology. 2014 Apr 25;3:e28497. eCollection 2014.

Secretory pathways generating immunosuppressive NKG2D ligands: New targets for therapeutic intervention.

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Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain.
Cellular Biology of Renal Diseases Laboratory; Instituto de Investigación Sanitaria Fundación Jiménez Díaz; Universidad Autónoma Madrid; Madrid, Spain.
Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain ; Fundación Renal "Iñigo Álvarez de Toledo"; Madrid, Spain.


Natural Killer Group 2 member D (NKG2D) activating receptor, present on the surface of various immune cells, plays an important role in activating the anticancer immune response by their interaction with stress-inducible NKG2D ligands (NKG2DL) on transformed cells. However, cancer cells have developed numerous mechanisms to evade the immune system via the downregulation of NKG2DL from the cell surface, including the release of NKG2DL from the cell surface in a soluble form. Here, we review the mechanisms involved in the production of soluble NKG2DL (sNKG2DL) and the potential therapeutic strategies aiming to block the release of these immunosuppressive ligands. Therapeutically enabling the NKG2D-NKG2DL interaction would promote immunorecognition of malignant cells, thus abrogating disease progression.


NKG2D; NKs; exosomes; shedding; soluble NKG2D ligands

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