Targeting NK-cell checkpoints for cancer immunotherapy
Muntasell A (1), Ochoa MC (2), Cordeiro L (2), Berraondo P (1), López-Díaz de Cerio A (3), Cabo M (1), López-Botet M (1), Melero I (4).
(1) Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
(2) Centro de Investigacion Medica Aplicada (CIMA), Pamplona, Spain.
(3) Departamento de Inmunologia e Inmunoterapia, Clinica Universidad de Navarra, Pamplona, Spain.
(4) Centro de Investigacion Medica Aplicada (CIMA), Pamplona, Spain; Departamento de Inmunologia e Inmunoterapia, Clinica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
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.
CITATION Curr Opin Immunol. 2017 Feb 22;45:73-81. doi: 10.1016/j.coi.2017.01.003