Activation of natural killer (NK) cell cytotoxicity requires adhesion and formation of a conjugate with a susceptible target cell, followed by actin polymerization, and polarization of the microtubule organizing center (MTOC) and cytolytic granules to the NK cell immune synapse. Here, by using the YTS NK cell line as a model, CD28 is shown to be an activating receptor. It signals cytotoxicity i...

Secretory lysosomes of natural killer (NK) cells, containing perforin and granzymes, are indispensable for NK-cell cytotoxicity because their release results in the induction of target-cell apoptosis. Lysosome-associated membrane protein (LAMP) 1/CD107a is used as a marker for NK-cell degranulation, but its role in NK-cell biology is unknown. We show that LAMP1 silencing causes inhibition of NK...

The poor outcome of advanced ovarian cancer under conventional therapy stimulated the exploration of new strategies to improve therapeutic efficacy. In our preclinical in vitro study we investigated a combination of targeted therapy and immunotherapy. Combination treatment with the anti-EGFR-antibody Cetuximab, related tyrosine kinase inhibitors (TKI) and cytolytic NK cells was tested against d...

The evolutionarily conserved YAP/TAZ mechano-responsive transcription cofactors regulate development and tumorigenesis. Here, we show for the first time that human natural killer (NK) cells specifically express TAZ but not YAP, serves to limit NK cytotoxicity. synthetic double-stranded RNA (dsRNA), hiltonol, was able trigger cytoplasmic compartmentalization of TAZ, which increased Mechanistical...

Activating receptors such as NKG2D and Ly49D mediate a multitude of effector functions including cytotoxicity and cytokine generation in NK cells. However, specific signaling events that are responsible for the divergence of distinct effector functions have yet to be determined. In this study, we show that lack of caspase recruitment domain-containing protein Bcl10 significantly affected recept...

Allogeneic umbilical cord blood haematopoietic stem cells (UCB-HSCs) can be transplanted into a host with the intact innate immunity with limited immuno-reaction, although the mechanisms remain unclear. The present studies aimed at investigating potential mechanisms of allogeneic UCB-HSCs escape from the cytolysis of natural killer (NK) cells. We compared UCB-HSCs ability to protect from NK-med...

Natural killer (NK) cells, which represent a small fraction of normal peripheral blood mononuclear cells, were purified by immunofluorescent cell sorting of NKH1+ cells. cytotoxicity of NKH1+ cells could be enhanced through activation by monoclonal antibodies (anti-T11(2) and anti-T11(3)) specific for epitopes of the sheep erythrocyte receptor or by recombinant interleukin-2 (rIL-2). After 18 h...

We measured natural killer (NK) cell cytotoxicity and cortisol and prolactin concentrations in peripheral venous blood samples obtained from pregnant Gabonese women at the time of delivery. The NK cell-mediated cytotoxicity against Plasmodium falciparum-infected erythrocytes in vitro was lower in samples obtained from primiparous women than in samples obtained from multiparous women; cortisol c...

Immunoligands for stimulatory natural killer (NK)-cell receptors can be targeted to the surface of malignant cells by fusing them to antibody fragments. Mimicking an "induced-self" phenotype, such recombinant immunoligands signal danger, trigger NK-cell cytotoxicity and synergistically enhance antibody-dependent cellular cytotoxicity. These findings may be translated into novel immunotherapeuti...

Natural killer (NK) cells, which represent a small fraction of normal peripheral blood mononuclear cells, were purified by immunofluorescent cell sorting of NKH1+ cells. Cytotoxicity of NKH1+ cells could be enhanced through activation by monoclonal antibodies (anti-T112 and anti-Ti13) specific for epitopes of the sheep erythrocyte receptor or by recombinant interleukin-2 (rIL2). After 18 h, inc...