Natural killer (NK) cells are important effector cells for innate immune reactions against viral infections and malignant cells [1
]. NK cell effector functions include cellular cytotoxicity and the secretion of cytokines and chemokines. They also fulfill a regulatory role by engaging in cross-talk with diverse cellular components of the immune system [2
]. NK cell cytotoxicity is regulated through the recognition of target cells by integrating positive and negative signals from activating and inhibitory receptor-ligand interactions [3
]. Many inhibitory NK cell receptors are specific for self-MHC class I and are important to ensure the self-tolerance of NK cells. Loss of MHC class I upon viral infection or malignant transformation can, therefore, result in the so-called “missing-self” reactivity of NK cells. NK cell activation is mediated by a variety of different surface receptors that can recognize specific ligands on transformed or infected cells. Interestingly, freshly isolated resting human NK cells can only be activated by triggering two or more activating receptors in combination [4
]. Therefore, all stimulatory receptors for natural cytotoxicity are considered to be coactivating. The only exception seems to be CD16, which is sufficient by itself to induce activation of resting NK cells.
NK cell adhesion to target cells is essential for enabling the interaction between NK cell receptors and their ligands within the immunological synapse and for the directed release of granules towards the attached target cell during NK cell cytotoxicity [5
]. NK cell adhesion is mediated by integrins such as LFA-1. The function of LFA-1 is regulated by “inside-out signaling”, where signals from other surface receptors influences the affinity of LFA-1 by inducing conformational changes of the molecule, and also affects the avidity of LFA-1 by driving mobility within the cell membrane [6
]. This results in clustering of LFA-1 at the site of the NK cell synapse. Adhesion is, therefore, a highly regulated and dynamic process necessary for the function of NK cells.
WF10, or Immunokine, is based on the chlorite ion matrix tetrachlorodecaoxygen and is currently being evaluated in various clinical indications including the adjuvant therapy of inoperable pancreatic cancer and various inflammatory conditions [7
]. WF10 is known to have various immunological effects by stimulating innate immune functions, while inhibiting adaptive immune functions [10
]. In contrast to control animals, sublethally irradiated rats treated with WF10 developed significantly less hematological or solid tumors than controls [11
]. This antitumor effect of WF10 could be explained by stimulating the innate natural cytotoxicity against tumors. We, therefore, investigate the effect of WF10 on NK cell cytotoxicity.