Utilization of mouse models to decipher natural killer cell biology and potential clinical applications

Sungur, Can M.; Murphy, William J.

doi:10.1182/asheducation-2013.1.227

Cited by 23 publications

(22 citation statements)

References 40 publications

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“…In that study, the repression was significant at relatively high concentrations of AMP-B (5–10 mg/L, approximately 5.4–10.8 µM), which is compatible with our results using human primary NK cells despite some differences in NK cell activation between mice and men [18,19]. Given the stimulation of NK cells by AMP-B at low concentrations [15,20], the effect of AMP-B on NK cell activation appears to be dose-dependent.…”

Section: Discussionsupporting

confidence: 91%

Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells

Kim

Choi

Park

et al. 2017

IJMS

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Immunomodulatory drugs (IMiDs) present one example of immunomodulatory agents that improve cancer immunotherapy. Based on the cytotoxic activity of natural killer (NK) cells against cancer cells, a high throughput screening method for the identification of novel immunomodulatory molecules with the potential to stimulate NK cell cytotoxicity against cancer cells was designed and tested using an approved drug library. Among the primary hit compounds, the anti-fungal drug amphotericin B (AMP-B) increased the cytotoxicity of NK cell line and human primary NK cells in a direct manner. The increase in NK cell activity was related to increased formation of NK-target cell conjugates and the subsequent granule polarization toward target cells. The results of the present study indicate that AMP-B could serve a dual function as an anti-fungal and immunomodulatory drug.

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Section: Discussionsupporting

confidence: 91%

Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells

Kim

Choi

Park

et al. 2017

IJMS

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“…Compared to T cells, the lifespan of an NK cell is proposed to be much shorter, although this topic remains an area of significant debate due to differences between humans and mouse models. Fundamental advances in the understanding of NK cell biology have been generated from mouse models (Sungur and Murphy, 2013), and while these advances have improved understanding of human NK cells, there are critical species differences that limit the application of murine data to human application, opening the door for novel immunocompetent models to study NK biology (Park et al, 2016;Canter et al, 2017). One of the most critical differences between mouse and human NK cells concerns the lifespan of an NK cell and the putative, long-lived "memory" NK cell.…”

Section: Memory Nk Cells and Dysfunctionmentioning

confidence: 99%

Characterizing the Dysfunctional NK Cell: Assessing the Clinical Relevance of Exhaustion, Anergy, and Senescence

Judge

Murphy

Canter

2020

Front. Cell. Infect. Microbiol.

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143

126

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There is a growing body of literature demonstrating the importance of T cell exhaustion in regulating and shaping immune responses to pathogens and cancer. Simultaneously, the parallel development of therapeutic antibodies targeting inhibitory molecules associated with immune exhaustion (such as PD-1, but also TIGIT, and LAG-3) has led to a revolution in oncology with dramatic benefits in a growing list of solid and hematologic malignancies. Given this success in reinvigorating exhausted T cells and the related anti-tumor effects, there are increasing efforts to apply immune checkpoint blockade to other exhausted immune cells beyond T cells. One approach involves the reinvigoration of "exhausted" NK cells, a non-T, non-B lymphoid cell of the innate immune system. However, in contrast to the more well-defined and established molecular, genetic, and immunophenotypic characteristics of T cell exhaustion, a consensus on the defining functional and phenotypic features of NK "exhaustion" is less clear. As is well-known from T cell biology, separate and distinct molecular and cellular processes including senescence, anergy and exhaustion can lead to diminished immune effector function with different implications for immune regulation and recovery. For NK cells, it is unclear if exhaustion, anergy, and senescence entail separate and distinct entities of dysfunction, though all are typically characterized by decreased effector function or proliferation. In this review, we seek to define these distinct spheres of NK cell dysfunction, analyzing how they have been shown to impact NK biology and clinical applications, and ultimately highlight key characteristics in NK cell function, particularly in relation to the role of "exhaustion."

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“…Interestingly, we did not observe a significant modulation of granzyme B or CD107a/LAMP1 expression in tumors isolated from BME treated mice as compared with the control group in the HNSCC syngeneic mouse model (data not shown). The role of NK cells in anti-tumor responses in vivo may be difficult to interpret due to the difference between human and mouse NK cells (29). Human NK cells can be subclassified based upon the level of expression of CD56.…”

Section: Discussionmentioning

confidence: 99%

Bitter Melon Enhances Natural Killer–Mediated Toxicity against Head and Neck Cancer Cells

Bhattacharya

Muhammad

Steele

et al. 2017

Cancer Prevention Research

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Natural Killer (NK) cells are one of the major components of innate immunity, with the ability to mediate antitumor activity. Understanding the role of NK cell mediated tumor killing in controling of solid tumor growth is still in the developmental stage. We have shown recently that bitter melon extract (BME) modulates the regulatory T cell (Treg) population in head and neck squamous cell carcinoma (HNSCC). However, the role of BME in NK cell modulation against HNSCC remains unknown. In this study, we investigated whether BME can enhance the NK cell killing activity against HNSCC cells. Our results indicated that treatment of human NK cell line (NK3.3) with BME enhances ability to kill HNSCC cells. BME increases granzyme B accumulation and translocation/accumulation of CD107a/LAMP1 in NK3.3 cells exposed to BME. Further, an increase in cell surface expression of CD16 and NKp30 in BME treated NK3.3 cells was observed when co-cultured with HNSCC cells. Collectively, our results demonstrated for the first time that BME augments NK cell mediated HNSCC killing activity, implicating an immunomodulatory role of BME.

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Utilization of mouse models to decipher natural killer cell biology and potential clinical applications

Cited by 23 publications

References 40 publications

Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells

Amphotericin B, an Anti-Fungal Medication, Directly Increases the Cytotoxicity of NK Cells

Characterizing the Dysfunctional NK Cell: Assessing the Clinical Relevance of Exhaustion, Anergy, and Senescence

Bitter Melon Enhances Natural Killer–Mediated Toxicity against Head and Neck Cancer Cells

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