NK Cells and Cancer

Abstract

In this review, we overview the main features and functions of NK cells, focusing on their role in cell-mediated immune response to tumor cells. In parallel, we discuss the information available in the field of NK cell receptors and offer a wide general overview of functional aspects of cell targeting and killing, focusing on the recent acknowledgments on the efficacy of NK cells after cytokine and mAb administration in cancer therapy. Since efficacy of NK cell-based immunotherapy has been proven in KIR-mismatch regimens or in TRAIL-dependent apoptosis, the ability to manipulate the balance of activating and inhibitory receptors on NK cells and of their cognate ligands, as well as the sensitivity of tumor cells to apoptosis, opens new perspectives for NK cell-based immunotherapy.

Natural killer cell immune escape in acute myeloid leukemia

“…The latter can be achieved by defects in the AML cell apoptosis machinery [52][53][54] and by altered expression or shedding of receptors involved in Fasand TNF-mediated killing, [55][56][57][58][59] two pathways used by NK cells to kill tumor cells. 60 In addition to NK cell abnormalities and AML cell escape mechanisms, the interaction of both cell types with other immune cells provides a third factor contributing towards immune escape ( Table 1). Next to their role in tumor surveillance and elimination, NK cells are important regulators of DC by killing immature DC to limit inflammation and inappropriate T cell tolerization.…”

Driving Natural Killer cells toward the melanoma tumor battlefield: Autophagy as a valuable therapeutic target

“…1 However, the clinical response to NK-based cancer immunotherapy is so far relatively low. 2 Several lines of evidence suggest that these limited clinical responses could be attributed to the fact that tumors are infrequently infiltrated by NK cells and that NK cells failed to reach the tumor bed.…”

Recruitment of activating NK‐cell receptors 2B4 and NKG2D to membrane microdomains in mammalian cells is dependent on their transmembrane regions

“…NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Membrane microdomains, also called lipid rafts, are defined as cholesterol-and sphingolipid-rich membrane domains that affect various cellular functions, such as signaling, protein sorting, or endocytosis [9,10].…”

“…However, either interfering with the association between NKG2D and DAP10, or mutating the transmembrane region of 2B4 impacted the recruitment of the receptors to detergentresistant membrane fractions and modulated the function of 2B4 in NK cells. Our data suggest a potential interaction between the transmembrane region of NK-cell receptors and membrane lipids as a molecular mechanism involved in determining the membrane confinement of activating NK-cell receptors.Keywords: 2B4 r Activating receptor r Lipid rafts r Membrane microdomains r NK cells r NKG2D r Signal transduction Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Correspondence: Prof. Carsten Watzl e-mail: watzl@ifado.de [4].…”

“…Keywords: 2B4 r Activating receptor r Lipid rafts r Membrane microdomains r NK cells r NKG2D r Signal transduction Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction NK cells are large, granular lymphocytes of the innate immune system that contribute to successful immune responses by killing virally infected or transformed cells and by producing various cytokines [1][2][3]. The function of NK cells is controlled by the integration of signals from activating and inhibitory surface receptors Correspondence: Prof. Carsten Watzl e-mail: watzl@ifado.de [4].…”