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 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 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.

A common pathway mediated through Toll-like receptors leads to T- and natural killer–cell immunosuppression

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1437-1447 ◽  
Author(s):  
Ilan Vaknin ◽  
Liora Blinder ◽  
Lynn Wang ◽  
Roi Gazit ◽  
Elena Shapira ◽  
...  
Keyword(s):  
Natural Killer ◽  
Chronic Inflammation ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune System ◽  
Suppressor Cells ◽  
Toll Like Receptors ◽  
Down Regulation ◽  
Myeloid Suppressor Cells ◽  
Adaptive Immune

Abstract T- and natural killer (NK)–cell immunosuppression associated with ζ-chain down-regulation has been described in cancer, autoimmune, and infectious diseases. However, the precise stimuli leading to this bystander phenomenon in such different pathogen-dependent and sterile pathologies remained unresolved. Here, we demonstrate that Toll-like receptors (TLRs) play a major role in the induction of innate and adaptive immune system suppression; repetitive administration of single TLR 2, 3, 4, or 9 agonists, which do not exhibit any virulent or immune invasive properties, was sufficient to induce a bystander NK- and T-cell immunosuppression associated with ζ-chain down-regulation mediated by myeloid suppressor cells, as observed in the course of active pathologies. We identified a 35-amino acid (aa) region within the ζ-chain as being responsible for its degradation under TLR-mediated chronic inflammation. Furthermore, we provide evidence that ζ-chain levels could serve as a biomarker for chronic inflammation-dependent immunosuppression. Thus, although acute TLR-mediated activation could be beneficial in clearing pathogens or may serve as an immune adjuvant, such activation could be detrimental under sustained conditions.

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 NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency

2021 ◽  
Author(s):  
Dominic Lenz ◽  
Jens Pahl ◽  
Fabian Hauck ◽  
Seham Alameer ◽  
Meena Balasubramanian ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune System ◽  
Target Cells ◽  
Multisystem Disorder ◽  
Adaptive Immune ◽  
B Cell Deficiency

Abstract Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.

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.

The role of Natural killer (NK) cells as APCs, Cytotoxicity, Immuno-regulatory in Innate and Adaptive immune as Potential Therapeutic and Preventive Target in Infectious Diseases

2021 ◽  
Vol 12 (04) ◽  
pp. 415-437
Author(s):  
Dr. Zelalem Kiros Bitsue
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Immune Regulation ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Adaptive Immune

Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, in producing cytokines and in providing co-stimulation to cells of the adaptive immune system.

scholarly journals Checkpoint Inhibitors and Engineered Cells: New Weapons for Natural Killer Cell Arsenal Against Hematological Malignancies

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1578
Author(s):  
Massimo Giuliani ◽  
Alessandro Poggi
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Activation ◽  
Hematological Malignancies ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Killer Cell ◽  
Immune Surveillance ◽  
Antigen Receptors

Natural killer (NK) cells represent one of the first lines of defense against malignant cells. NK cell activation and recognition are regulated by a balance between activating and inhibitory receptors, whose specific ligands can be upregulated on tumor cells surface and tumor microenvironment (TME). Hematological malignancies set up an extensive network of suppressive factors with the purpose to induce NK cell dysfunction and impaired immune-surveillance ability. Over the years, several strategies have been developed to enhance NK cells-mediated anti-tumor killing, while other approaches have arisen to restore the NK cell recognition impaired by tumor cells and other cellular components of the TME. In this review, we summarize and discuss the strategies applied in hematological malignancies to block the immune check-points and trigger NK cells anti-tumor effects through engineered chimeric antigen receptors.

Sign in / Sign up

Export Citation Format

Share Document