Models to Study NK Cell Biology and Possible Clinical Application

Zamora, Anthony E.; Grossenbacher, Steven K.; Aguilar, Ethan G.; Murphy, William J.

doi:10.1002/0471142735.im1437s110

Cited by 23 publications

(21 citation statements)

References 39 publications

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“…(43) However, an evolving picture of NK cells is emerging highlighted by diverse subsets with different physiology and effector functions including cytotoxicity, cytokine production, and immune-editing(44). Key studies have demonstrated that NK cells are significantly more complex and more heterogeneous than the classic view of NK cells suggests (45).…”

Section: Bodymentioning

confidence: 99%

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Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy

Luna

Grossenbacher

Murphy

et al. 2016

Expert Opinion on Biological Therapy

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Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells.

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Section: Bodymentioning

confidence: 99%

“…Due to their localization in lymph nodes combined with their high cytokine production, a growing consensus is emerging that CD56 bright cells function as immune regulators, for example by modulating dendritic cell antigen presentation and by priming T cells toward a Th1 phenotype. (43)…”

Section: Bodymentioning

confidence: 99%

Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy

Luna

Grossenbacher

Murphy

et al. 2016

Expert Opinion on Biological Therapy

Self Cite

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“…Like NK cells, activated NKT cells release in the extracellular compartment pro- and anti-inflammatory cytokines/chemokines with the function of regulating the immune response ( 8 ). The activation of NK and NKT cells derives from the balance of signals coming from activatory and inhibitory receptors ( 9 , 10 ). There are some evidences about the possible involvement of NK and NKT cells in the pathogenesis of BD, but there is a discrepancy in the data.…”

Section: Introductionmentioning

confidence: 99%

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

et al. 2018

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Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis.

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“…Subsequent studies by the same group found this was in fact due to activated T cells expressing ASGM1 (23). Even NK1.1, a marker commonly used to deplete NK cells that is more specific, is expressed on other cell types (2). To label an agent as NK specific in mice has always been problematic, particularly in the case in which T cells can be affected, and necessitates the need for T cell-deficient mice and/or adoptive transfer studies using purified NK cells.…”

Section: Involvement Of Pd-1 Pathway and Nk Cells In Cancermentioning

confidence: 99%

NK cells for PD-1/PD-L1 blockade immunotherapy: pinning down the NK cell

Dunai¹,

Murphy²

2018

Journal of Clinical Investigation

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In spite of a very robust body of literature and definitive data demonstrating the importance of the programmed cell death receptor-1 (PD-1) pathway in T cells and their function, the data on NK cell PD-1 expression have been highly variable and, particularly in the case of mouse NK cells, scarce. In this issue of the JCI, Hsu et al. present data demonstrating PD-1 expression on mouse NK cells only within tumors and show that PD-1 blockade elicits an antitumor NK cell-mediated response. This study indicates that, given the complexity of both the biology and study of NK cells, further work is needed to more clearly determine the role of the PD-1/PD-1 ligand (PD-L1) on NK cells.

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Models to Study NK Cell Biology and Possible Clinical Application

Cited by 23 publications

References 39 publications

Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy

Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

NK cells for PD-1/PD-L1 blockade immunotherapy: pinning down the NK cell

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