Figure 1.

A dysfunctional or exhausted NK cell may be characterised by more than an alteration of surface receptor expression. Functionally impaired NK cells are commonly observed in cancer to exhibit reduced anti-tumour activity, including secretion of cytokines and cytotoxic molecules. There is currently a lack of consensus as to what constitutes an exhausted NK cell. NK cell dysfunction exists over a spectrum, and various aspects that may define exhaustion have been researched thus far. Beyond the well-discussed upregulation of inhibitory receptors such as TIGIT, NKG2A, and downregulation of activating receptors such as NKG2D, DNAM-1, we propose that the exhausted NK cell can also be marked by the altered expression of the T-box transcription factors, T-bet and Eomes. Additionally, exhausted NK cells exhibit a phenotype resembling that of the less cytotoxic ILC1 cells, which are additionally marked by the expression of CD49a.