Increased NK cell immunity in a transgenic mouse model of NKp46 overexpression

Glasner, Ariella; Isaacson, Batya; Viukov, Sergey; Neuman, Tzahi; Friedman, Nehemya; Mandelboim, Michal; Sexl, Veronika; Hanna, Jacob; Mandelboim, Ofer

doi:10.1038/s41598-017-12998-w

Cited by 17 publications

(14 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a downmodulation of NKp46 upon IL-15 exposure. This is in accordance with previous reports (50) and is troublesome, given the importance of this receptor in NK cell antiviral activity (22,51,52). Therefore, and even if we observed an important improvement in NK cell function despite NKp46 downmodulation, it might be of interest to consider a complementary strategy to boost NKp46 expression, thus further increasing NK cell antiviral function.…”

Section: Discussionsupporting

confidence: 92%

Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo

Garrido

Abad-Fernández

Tuyishime

et al. 2018

J Virol

110

106

View full text Add to dashboard Cite

Current efforts toward human immunodeficiency virus (HIV) eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8 T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of interleukin 15 (IL-15) treatment on NK cell function and the potential for stimulated NK cells to clear the HIV reservoir. We measured NK cell receptor expression, antibody-dependent cell-mediated cytotoxicity (ADCC), cytotoxicity, interferon gamma (IFN-γ) production, and antiviral activity in autologous HIV replication systems. All NK cell functions were uniformly improved by IL-15, and, more importantly, IL-15-treated NK cells were able to clear latently HIV-infected cells after exposure to vorinostat, a clinically relevant latency-reversing agent. We also demonstrate that NK cells from HIV-infected individuals aviremic on antiretroviral therapy can be efficiently stimulated with IL-15. Our work opens a promising line of investigation leading to future immunotherapies to clear persistent HIV infection using NK cells. In the search for an HIV cure, strategies to enhance immune function to allow recognition and clearance of HIV-infected cells following latency reversal are being evaluated. Natural killer (NK) cells possess characteristics that can be exploited for immunotherapy against persistent HIV infection. We demonstrate that NK cells from HIV-positive donors can be strongly stimulated with IL-15, improving their antiviral and cytotoxic potential and, more importantly, clearing HIV-infected cells after latency reversal with a clinically relevant drug. Our results encourage further investigation to design NK cell-based immunotherapies to achieve HIV eradication.

show abstract

Section: Discussionsupporting

confidence: 92%

Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo

Garrido

Abad-Fernández

Tuyishime

et al. 2018

J Virol

110

106

View full text Add to dashboard Cite

show abstract

“…For example, genetic deficiency of NKp46 in mice results in the impaired clearance of subcutaneous T lymphoma (95) and melanoma (96) tumors and melanoma lung metastases (97, 98). Moreover, transgenic overexpression of NKp46 resulted in the enhanced clearance of melanoma lung metastases (99). Intriguingly, enhanced NKp46 signaling elicited IFN-γ secretion and increased tumor deposition of fibronectin, which altered the solid tumor architecture and resulted in the decreased formation of melanoma metastases (100).…”

Section: Ncrs and Their Ligands In Cancermentioning

confidence: 99%

“…However, it is also possible that the NCRs may regulate other anti-tumor pathways. For melanoma metastases, NK cells were attributed to play a major role (99). However, ILC1 are phenotypically closely related to conventional NK cells as both these cell-types express T-bet and secrete IFN-γ (132, 133).…”

Section: Ncr-mediated Control Of Tumoricidal Pathwaysmentioning

confidence: 99%

The Natural Cytotoxicity Receptors in Health and Disease

2019

View full text Add to dashboard Cite

The Natural Cytotoxicity Receptors (NCRs), NKp46, NKp44, and NKp30, were some of the first human activating Natural Killer (NK) cell receptors involved in the non-MHC-restricted recognition of tumor cells to be cloned over 20 years ago. Since this time many host- and pathogen-encoded ligands have been proposed to bind the NCRs and regulate the cytotoxic and cytokine-secreting functions of tissue NK cells. This diverse set of NCR ligands can manifest on the surface of tumor or virus-infected cells or can be secreted extracellularly, suggesting a remarkable NCR polyfunctionality that regulates the activity of NK cells in different tissue compartments during steady state or inflammation. Moreover, the NCRs can also be expressed by other innate and adaptive immune cell subsets under certain tissue conditions potentially conferring NK recognition programs to these cells. Here we review NCR biology in health and disease with particular reference to how this important class of receptors regulates the functions of tissue NK cells as well as confer NK cell recognition patterns to other innate and adaptive lymphocyte subsets. Finally, we highlight how NCR biology is being harnessed for novel therapeutic interventions particularly for enhanced tumor surveillance.

show abstract

“…It is well established that activated NK cells destroy tumor cells mainly via cytotoxicity effector molecules, including granzyme B, perforin, IFN-γ and TNF-α ( 28 ). The results of flow cytometry revealed that the expression of granzyme B and IFN-γ was significantly increased following incubation with propofol ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Propofol improves the function of natural killer cells from the peripheral blood of patients with esophageal squamous cell carcinoma

et al. 2018

View full text Add to dashboard Cite

Postoperative immunosuppression is associated with the recurrence and metastasis of esophageal squamous cell carcinoma (ESCC). Propofol is a commonly used intravenous anesthetic and has been reported to be associated with immunosuppression; however, little is known about its effect on innate immune cells during the postoperative period in patients with ESCC. The aim of the present study was to investigate the effects of propofol on the phenotype and cytotoxicity of natural killer (NK) cells derived from the peripheral blood of patients with ESCC. The percentage, phenotype and function of NK cells were compared between patients with ESCC and healthy volunteers using flow cytometry. NK cells were negatively sorted using magnetic beads and cocultured with propofol to assess changes in phenotype and function. The results revealed that the percentage of NK cells was significantly increased in the peripheral blood of patients with ESCC, while their activity and cytotoxicity were impaired. NK cells were successfully separated from peripheral blood in vitro and it was demonstrated that propofol enhanced their activity by influencing the expression of activating or inhibitory receptors. Furthermore, propofol was able to increase the cytotoxicity of NK cells from the peripheral blood of patients with ESCC. These results suggest that propofol is able to improve the function of NK cells in patients with ESCC and may therefore be an appropriate anesthetic for ESCC surgery.

show abstract

Increased NK cell immunity in a transgenic mouse model of NKp46 overexpression

Cited by 17 publications

References 59 publications

Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo

Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo

The Natural Cytotoxicity Receptors in Health and Disease

Propofol improves the function of natural killer cells from the peripheral blood of patients with esophageal squamous cell carcinoma

Contact Info

Product

Resources

About