NK cell study highlights potential therapeutic target in immuno-oncology

The DNAM-1 receptor – an activating protein present on the surface of NK cells – has been demonstrated to play a key role in the promotion of NK cell-mediated cancer cell elimination. The mechanism of action was uncovered by a team at The Clinical Research Institute of Montreal (IRCM; Canada) and details appeared yesterday in the Journal of Experimental Medicine.

NK cells are crucial in immune surveillance and elimination of cancer cells – a process that this study shows to be at least in part stimulated by the DNAM-1 upon recognition of its ligands CD155 and CD112. The study also found that DNAM-1 competes for cancer cell interaction with other surface receptors such as the TIGIT receptor.

“When the TIGIT receptor interacts with an infected cell, it prevents its interaction with the DNAM-1 protein, which, as a result, suppresses the function of NK cells and slows the immune system,” explained team lead André Veillette (IRCM).

It is this competition with TIGIT that led the team to propose a new target for novel immune-oncology treatments. As Veillette reported: “Our results reveal how antibodies against TIGIT could become new therapies in immune-oncology. These antibodies could improve the function of the DNAM-1 protein, thereby improving the ability of NK cells to destroy tumour cells. This type of therapy could have a significant impact on the next generation of cancer treatments.”

Sources: Zhang Z, Wu N, Lu Y, Davidson D, Colonna M, Veillette A. DNAM-1 controls NK cell activation via an ITT-like motif. J Exp Med. 212, 2165–2182 (2015); IRCM press release