NK cell differentiation mainly occurs in the bone marrow (BM) where a critical role in the regulation of developing lymphocyte distribution is played by members of the chemokine receptor family. In mouse, the chemokine receptor CX3CR1 identifies a late stage of NK cell development characterized by decreased effector functions and expression of the inhibitory receptor KLRG1. The role of CX3CR1 i...

Natural killer (NK) cells are a gatekeeper of the body’s innate defense system against cancers and infections. A growing body literature from us others finds that NK promote anti-cancer immune surveillance, defects in cell development associated with poor clinical prognosis cancers. In preclinical studies, were found to drive tumor regression delay relapse. Because potentially less damaging eas...

DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to pro...

Many chemokine receptors are typically found on natural killer cells, including CX3CR1, the receptor for the chemokine Fractalkine (FKN). This study explored whether interaction between CX3CR1 and FKN is relevant for NK cell functions in cytotoxicity against tumors. FKN expression was examined by polymerase chain reaction and CX3CR1 expression in NK cells was analyzed by flow cytometry. NK cell...

Natural killer (NK) cells exert a crucial role in early immune responses as a major innate effector component. However, the underlying mechanisms of NK cell development remain largely elusive. Here we show that robust autophagy appears in the stage of immature NK cells (iNKs), which is required for NK cell development. Autophagy defects result in damaged mitochondria and accumulation of reactiv...

BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effec...

Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (IL-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensi...

Abstract Background: Cure rates for osteosarcoma (OS) have not improved in >30 years and no new effectivetherapies been identified metastatic disease. Natural killer (NK) cells become an attractive tool cancer immunotherapy. Efficay is by direct tumor targeting introducing a specific chimeric antigen receptor (CAR). Emerging knowledge suggests CD70 to be viable candidate as expression hi...