scholarly journals Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Cancer Survivors ◽  
Nk Cells ◽  
Natural Killer ◽  
Acute Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Current Evidence ◽  
Cell Mobilization

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.

scholarly journals Generation of Natural Killer Cell Memory during Viral Infection

2015 ◽  
Vol 7 (6) ◽  
pp. 557-562 ◽  
Author(s):  
Timothy E. O'Sullivan ◽  
Joseph C. Sun
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune System ◽  
Current Evidence ◽  
Cell Memory ◽  
Independent Manner ◽  
Adaptive Immune

Immunological memory is classically regarded as an attribute of antigen-specific T and B lymphocytes of the adaptive immune system. Cells of the innate immune system, including natural killer (NK) cells, have been considered short-lived cytolytic cells that can rapidly respond against pathogens in an antigen-independent manner and then die off. However, NK cells have recently been described to possess traits of adaptive immunity, such as clonal expansion after viral antigen exposure to generate long-lived memory cells. In this review, we will discuss the current evidence for viral-induced NK cell memory in both mice and humans.

scholarly journals Natural Killer Cells: The Linchpin for Successful Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Kari A. Shaver ◽  
Tayler J. Croom-Perez ◽  
Alicja J. Copik
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Natural Killer ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Current Evidence ◽  
Cell Therapies

Cancer immunotherapy is a highly successful and rapidly evolving treatment modality that works by augmenting the body’s own immune system. While various immune stimulation strategies such as PD-1/PD-L1 or CTLA-4 checkpoint blockade result in robust responses, even in patients with advanced cancers, the overall response rate is low. While immune checkpoint inhibitors are known to enhance cytotoxic T cells’ antitumor response, current evidence suggests that immune responses independent of cytotoxic T cells, such as Natural Killer (NK) cells, play crucial role in the efficacy of immunotherapeutic interventions. NK cells hold a distinct role in potentiating the innate immune response and activating the adaptive immune system. This review highlights the importance of the early actions of the NK cell response and the pivotal role NK cells hold in priming the immune system and setting the stage for successful response to cancer immunotherapy. Yet, in many patients the NK cell compartment is compromised thus lowering the chances of successful outcomes of many immunotherapies. An overview of mechanisms that can drive NK cell dysfunction and hinder immunotherapy success is provided. Rather than relying on the likely dysfunctional endogenous NK cells to work with immunotherapies, adoptive allogeneic NK cell therapies provide a viable solution to increase response to immunotherapies. This review highlights the advances made in development of NK cell therapeutics for clinical application with evidence supporting their combinatorial application with other immune-oncology approaches to improve outcomes of immunotherapies.

Mechanisms of Natural Killer Cell Evasion Through Viral Adaptation

2020 ◽  
Vol 38 (1) ◽  
pp. 511-539
Author(s):  
Mathieu Mancini ◽  
Silvia M. Vidal
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Target Cells ◽  
Activating Receptors ◽  
Viral Adaptation ◽  
Antiviral Function

The continuous interactions between host and pathogens during their coevolution have shaped both the immune system and the countermeasures used by pathogens. Natural killer (NK) cells are innate lymphocytes that are considered central players in the antiviral response. Not only do they express a variety of inhibitory and activating receptors to discriminate and eliminate target cells but they can also produce immunoregulatory cytokines to alert the immune system. Reciprocally, several unrelated viruses including cytomegalovirus, human immunodeficiency virus, influenza virus, and dengue virus have evolved a multitude of mechanisms to evade NK cell function, such as the targeting of pathways for NK cell receptors and their ligands, apoptosis, and cytokine-mediated signaling. The studies discussed in this article provide further insights into the antiviral function of NK cells and the pathways involved, their constituent proteins, and ways in which they could be manipulated for host benefit.

scholarly journals The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans

2009 ◽  
Vol 206 (7) ◽  
pp. 1495-1503 ◽  
Author(s):  
Cameron S. Brandt ◽  
Myriam Baratin ◽  
Eugene C. Yi ◽  
Jacob Kennedy ◽  
Zeren Gao ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Tumor ◽  
Cell Surface Molecule ◽  
B7 Family

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.

scholarly journals The role of cytokine in regulation of the natural killer cell activity

2008 ◽  
Vol 136 (7-8) ◽  
pp. 423-429 ◽  
Author(s):  
Vladimir Jurisic ◽  
Sladjana Stojacic-Djenic ◽  
Natasa Colovic ◽  
Gordana Konjevic
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Target Cells

Natural killer (NK) cells are characterized by a CD3-CD16+ CD56+ immunophenotype and have a central role in the innate immune system. They are defined by their capacity to kill certain tumor-target cells or virus infected cells without prior sensitization or MHC-restriction. The activity of the NK cells is determined by the balance between activation and inhibitory receptor molecules expressed on the surface of NK cells. However, several cytokines and chemokines can significantly modulate their activity, inducing increase of NK cell activity. Immunomodulation mediated by NK cells is very important mechanism in tumor immunity, as well as in other immunodepressions of the immune system. In this study, we summarize the role of several cytokines, including IFN, IL-1, IL-2, IL-4, IL-7, IL-12 and IL-17, on NK cell function. The NK cells, after activation, depending on cytokine environment, can differentiate into NK1 cells that produce Th1 cytokine type (IFN-?, IL-2, IL-12) or NK2 cells that produce Th2 type cytokines, enhance exocytosis and release of previously formed molecules from NK cells (granzyme, perforin). We also describe that the release of cytokines and mediators show local or distance effects, or induce apoptosis (mostly by secreted TNF-?) after binding appropriated killer cell receptors from TNF receptor superfamily.

scholarly journals Natural killer cell mobilization and egress following acute exercise in men with prostate cancer

2020 ◽  
Vol 105 (9) ◽  
pp. 1524-1539
Author(s):  
Erik D. Hanson ◽  
Samy Sakkal ◽  
Shadney Que ◽  
Eunhan Cho ◽  
Guillaume Spielmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Acute Exercise ◽  
Killer Cell ◽  
Cell Mobilization

scholarly journals Stat5b Is Essential for Natural Killer Cell–mediated Proliferation and Cytolytic Activity

1998 ◽  
Vol 188 (11) ◽  
pp. 2067-2074 ◽  
Author(s):  
Kazunori Imada ◽  
Eda T. Bloom ◽  
Hiroshi Nakajima ◽  
Judith A. Horvath-Arcidiacono ◽  
Garry B. Udy ◽  
...  
Keyword(s):  
Immune System ◽  
Natural Killer Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cytolytic Activity ◽  
High Dose ◽  
Β Chain ◽  
Deficient Mice

We have analyzed the immune system in Stat5-deficient mice. Although Stat5a−/− splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b−/− splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor β chain (IL-2Rβ), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation in activated splenocytes, freshly isolated splenocytes from Stat5b−/− mice exhibited greatly diminished proliferation in response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2– and IL-15–mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell–mediated proliferation and cytolytic activity.

Alterations of natural killer cell receptors as biomarkers associated with the severity of the disease in prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15155-e15155
Author(s):  
Christine Pasero ◽  
Gwenaelle Gravis ◽  
Palma Rocchi ◽  
Sylvaine Just-Landi ◽  
Philippe Livrati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Metastatic Breast ◽  
Prostate Tumor ◽  
Metastatic Progression ◽  
Pronounced Increase

e15155 Background: Recently, therapeutic vaccines and monoclonal antibody-based therapies have been investigated as promising new treatments against prostate cancer (PC). Natural killer (NK) cells which have anti-tumoral activity thus represent promising candidates for immunotherapy. Our group have reported major impairments of NK in acute myeloid leukemia and recently in metastatic breast cancer. The aim of this work was to evaluate the phenotype and function of NK cells in patients with localized and metastatic PC to determine their role in disease progression. Methods: Activating and inhibitory receptors were analyzed in peripheral NK cells from 14 patients with localized PC, 33 with metastatic disease and 30 healthy donors. NK function was evaluated by measuring CD107 degranulation. Results: The ratio mean fluorescence intensity RMFI (MFI receptor/MFI control isotype) of the activating receptor NKp30 was significantly lower in patients (7.30 +/- 0.68, p=0.0059) than in HD (10.99 +/- 1.34), whereas NKp46 was lower in the metastatic patients only (11.76 +/- 1.18) compared to the localized cases (21.86 +/- 4.25) and HD (19.13 +/- 2.39). The RMFI of 2B4 (47.14 +/- 7.99), the percentage of positive cells for the inhibitory receptor ILT2 (49.34 +/- 3.90, p=0.0003) and the maturation marker CD57 (41.13 +/- 4.69, p=0.0014) were significantly upregulated in patients compared with HD (2B4 23.09 +/- 4.74, ILT2 20.65 +/- 3.09, CD57 21.36 +/- 3.07), with a more pronounced increase in the metastatic groups. The RMFI of other receptors such as NKG2D or CD94 does not differ. NK cells from patients were significantly less effective (17.90% +/- 1.48, p<0.0001) than NK from HD (30.31% +/- 2.70) to degranulate against the K562 target or prostate tumor cell lines. Conclusions: We observed an altered phenotype of NK cells in PC, correlated with decreased NK cell function, with alterations more pronounced during metastatic progression. Prostate tumor cells could have the ability to impair NK cell visibility through the modulation of their receptors and consequently decrease their cytotoxic function. This highlights the possibility of restoring NK cells cytotoxicity as a future therapy against PC.

scholarly journals The role of natural killer cell in gastrointestinal cancer: killer or helper

Oncogene ◽  
2020 ◽  
Author(s):  
Feixue Wang ◽  
Jennie Ka Ching Lau ◽  
Jun Yu
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Gastrointestinal Cancer ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Killer Cell ◽  
Adaptive Immune System ◽  
High Morbidity ◽  
Adaptive Immune

AbstractGastrointestinal cancer is one of the leading health problems worldwide, with a high morbidity and mortality. To date, harnessing both the innate and adaptive immune system against cancer provides a selective and effective therapeutic strategy for patients. As a first line defense against cancer, natural killer (NK) cells can swiftly target and lyse tumor cells without prior activation. In addition to its pivotal role in innate immunity, NK cells also play unique roles in the adaptive immune system as it enhance anti-tumor adaptive immune responses through secretion of cytokines and retaining an immunological memory. All these characteristics make NK cell a promising anti-cancer agent for patients. In spite of scarce infiltration and impaired function of NK cells in tumors, and the fact that tumors easily develop resistant mechanisms to evade the attacks from endogenous NK cells, multiple strategies have been developed to boost anti-tumor effect of NK cells and abolish tumor resistance. Some examples include adoptive transfer of NK cells after ex vivo activation and expansion; restoration of NK cell function using immune checkpoint inhibitors, and monoclonal antibody or cytokine treatment. Preclinical data have shown encouraging results, suggesting that NK cells hold great potential in cancer therapy. In this review, we discuss NK cells’ cytotoxicity and modulation function in GI cancer and the current application in clinical therapy.

scholarly journals Natural killer cell activation after infection with lactate dehydrogenase-elevating virus

2002 ◽  
Vol 83 (11) ◽  
pp. 2709-2716 ◽  
Author(s):  
Dominique Markine-Goriaynoff ◽  
Xavier Hulhoven ◽  
César L. Cambiaso ◽  
Philippe Monteyne ◽  
Thérèse Briet ◽  
...  
Keyword(s):  
Immune System ◽  
Lactate Dehydrogenase ◽  
Nk Cells ◽  
Natural Killer ◽  
Innate Immune System ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Innate Immune ◽  
Ifn Γ

Early after infection, lactate dehydrogenase-elevating virus (LDV) alters the immune system by polyclonally activating B lymphocytes, which leads to IgG2a-restricted hypergammaglobulinaemia, and by suppressing the secretion of Th2 cytokines. Considering that these alterations may involve cells of the innate immune system and cytokines such as interferon-gamma (IFN-γ), we analysed the effect of LDV on natural killer (NK) cells. Within a few days of infection, a strong and transient NK cell activation, characterized by enhanced IFN-γ message expression and cytolysis, was observed. LDV triggered a large increase in serum IFN-γ levels. Because NK cells and IFN-γ may participate in the defence against virus infection, we analysed their possible role in the control of LDV titres with a new agglutination assay. Our results indicate that neither the activation of NK cells nor the IFN-γ secretion affect the early and rapid virus replication that follows LDV inoculation.

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