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

摘要

Natural Killer Group 2 member D (NKG2D) activatingreceptor, present on the surface of various immune cells,plays an important role in activating the anticancer immuneresponse by their interaction with stress-inducible NKG2Dligands (NKG2DL) on transformed cells. However, cancercells have developed numerous mechanisms to evade theimmune system via the downregulation of NKG2DL from thecell surface, including the release of NKG2DL from the cellsurface in a soluble form. Here, we review the mechanismsinvolved in the production of soluble NKG2DL (sNKG2DL)and the potential therapeutic strategies aiming to block therelease of these immunosuppressive ligands. Therapeuticallyenabling the NKG2D-NKG2DL interaction would promoteimmunorecognition of malignant cells, thus abrogatingdisease progression.