Targeting NK-cell checkpoints for cancer immunotherapy

- NK cells are cytotoxic lymphocytes with potential for cancer immunotherapy.
- NK-cell numbers and function are regulated by surface receptors and cytokines.
- Inhibitory and activating NK-cell receptors can be targeted for cancer immunotherapy.
- IL-2 and IL-15 enhance NK-cell anti-tumor function.
- Strengthening NK-cell ADCC emerges as a suitable approach for cancer treatment.

Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities. These agents can be used to potentiate NKcell- mediated antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated tumor cells, offering potential for multiple combinatorial immunotherapy strategies against cancer.