scholarly journals Human natural killer cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Michael A. Caligiuri
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Cell Receptor ◽  
Human Malignancy ◽  
Human Natural Killer Cells ◽  
Receptor Biology ◽  
Granular Lymphocytes

Abstract Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.

scholarly journals A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killer-sensitive tumor cell, K562.

1985 ◽  
Vol 161 (6) ◽  
pp. 1464-1482 ◽  
Author(s):  
J H Phillips ◽  
L L Lanier
Keyword(s):  
T Lymphocytes ◽  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Human Natural Killer Cells ◽  
Vitro Model ◽  
Granular Lymphocytes ◽  
Leu 7

A subpopulation of low density granular lymphocytes that express the natural killer (NK) cell-associated Leu-11 antigen (IgG Fc receptor) were stimulated directly by coculture with an NK-sensitive tumor cell, K562. T lymphocytes (Leu-11-) responded only weakly when cocultured with K562. The response of Leu-11+ cells apparently did not require exogeneous factors or accessory cells. The K562-activated cells retained expression of Leu-11 antigen, acquired activation antigens, and were highly cytotoxic against NK-sensitive and -insensitive tumor cells. Anti-IL-2 receptor monoclonal antibody minimally inhibited the activation of Leu-11+ cells by K562, but completely inhibited the phytohemagglutinin-induced activation of the Leu-11- cells from the same individual. Leu-11+ cells can be divided into Leu-7-11+ and Leu-7+11+ subpopulations using anti-Leu-7 antibody. These subsets were separated by two-color fluorescence-activated cell sorting and cocultured with K562. Proliferation by Leu-7-11+ cells was significantly greater than by Leu-11+7+ cells. Leu-7+11- granular lymphocytes and T lymphocytes (Leu-7-11-) typically proliferated only weakly when cocultured with K562. A proportion of the Leu-7-11+ cells acquired Leu-7 antigen after stimulation with K562, whereas the phenotype of Leu-7+11+, Leu-7+11-, and Leu-7-11- subsets was unaffected. These results demonstrate a developmental relationship between the Leu-7-11+ and Leu-7+11+ lymphocytes and suggest that Leu-7 antigen may be expressed late in the differentiation pathway of NK cells. The direct activation of highly purified Leu-11+ cells by coculture with K562 provides an in vitro model with which to study the activation and maturation of human NK cells.

scholarly journals Aneuploid cells activate NF-κB to promote their immune clearance by NK cells

2020 ◽  
Author(s):  
Ruoxi W. Wang ◽  
Sonia Viganò ◽  
Uri Ben-David ◽  
Angelika Amon ◽  
Stefano Santaguida
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Cancer Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Immune Recognition ◽  
Immune Clearance

SummaryThe immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance is thus critical for understanding how cancer cells are recognized and eliminated. We previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by Natural Killer (NK) cells in vitro. Here we show that this is also true for aneuploid untransformed cells that had not lost their ability to proliferate. Their elimination by NK cells, like that of aneuploid senescent cells, is predominantly mediated by non-cell autonomous mechanisms. Our data further indicate that NF-κB signaling in aneuploid cells is central to eliciting this immune response. Inactivating NF-κB abolishes NK-cell mediated clearance in aneuploid cells in vitro. In cancer cell lines, NF-κB signaling correlates with degree of aneuploidy, raising the possibility that aneuploidy-induced immune recognition is partially retained in cancer.

scholarly journals CRISPR-Cas9–Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3489
Author(s):  
Takayuki Morimoto ◽  
Tsutomu Nakazawa ◽  
Ryosuke Matsuda ◽  
Fumihiko Nishimura ◽  
Mitsutoshi Nakamura ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Protein Complexes ◽  
Lymphocyte Activation ◽  
Exon 2 ◽  
Effector Cells ◽  
Guide Rna ◽  
Human Natural Killer Cells

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell–mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.

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 Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Reza Hosseini ◽  
Hamzeh Sarvnaz ◽  
Maedeh Arabpour ◽  
Samira Molaei Ramshe ◽  
Leila Asef-Kabiri ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Clinical Significance ◽  
Surveillance System ◽  
Cancer Biology ◽  
Nk Cell ◽  
Ex Vivo ◽  
Immune Surveillance ◽  
Tumor Development ◽  
Cell Responses

AbstractTumor-derived exosomes (TDEs) play pivotal roles in several aspects of cancer biology. It is now evident that TDEs also favor tumor growth by negatively affecting anti-tumor immunity. As important sentinels of immune surveillance system, natural killer (NK) cells can recognize malignant cells very early and counteract the tumor development and metastasis without a need for additional activation. Based on this rationale, adoptive transfer of ex vivo expanded NK cells/NK cell lines, such as NK-92 cells, has attracted great attention and is widely studied as a promising immunotherapy for cancer treatment. However, by exploiting various strategies, including secretion of exosomes, cancer cells are able to subvert NK cell responses. This paper reviews the roles of TDEs in cancer-induced NK cells impairments with mechanistic insights. The clinical significance and potential approaches to nullify the effects of TDEs on NK cells in cancer immunotherapy are also discussed.

Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3146-3151 ◽  
Author(s):  
Megan A. Cooper ◽  
Todd A. Fehniger ◽  
Sarah C. Turner ◽  
Kenneth S. Chen ◽  
Bobak A. Ghaheri ◽  
...  
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Natural Killer ◽  
Innate Immune Response ◽  
Nk Cell ◽  
Primary Source ◽  
Interferon Γ ◽  
Innate Immune ◽  
Immunoregulatory Cytokines ◽  
Human Natural Killer Cells

Abstract During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56bright and CD56dim). In this report, it is shown that CD56bright NK cells produce significantly greater levels of interferon-γ, tumor necrosis factor-β, granulocyte macrophage–colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56dim NK cells, which produce negligible amounts of these cytokines. Further, qualitative differences in CD56bright NK-derived cytokines are shown to be dependent on the specific monokines present. For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56bright NK cells. It is proposed that human CD56bright NK cells have a unique functional role in the innate immune response as the primary source of NK cell–derived immunoregulatory cytokines, regulated in part by differential monokine production.

scholarly journals Generation of human natural killer cells from immature progenitors does not require marrow stromal cells

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 841-846 ◽  
Author(s):  
MR Silva ◽  
R Hoffman ◽  
EF Srour ◽  
JL Ascensao
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Peripheral Blood Mononuclear ◽  
Specific Lysis ◽  
Human Natural Killer Cells

Abstract Human natural killer (NK) cells comprise 10% to 15% of peripheral blood mononuclear cells and have an important role in immune responses against tumors, viral infections, and graft rejection. NK cells originate in bone marrow (BM), but their progenitors and lineage development have not been completely characterized. We studied the generation of NK cells from purified CD34+HLADR- and CD34+HLADR+ BM progenitors and the influence of various cytokines on their production. We show that CD3-CD56+ cytotoxic NK cells can develop from both progenitors populations when interleukin-2 (IL-2) is present in an in vitro suspension culture system containing IL-1 alpha and stem cell factor. Up to 83.8% and 98.6% CD3-CD56+ cells were detected in CD34+HLADR- and CD34+DR+ cultures, respectively, after 5 weeks of culture; significant numbers of NK cells were first detected after 2 weeks. Cytotoxic activity paralleled NK cell numbers; up to 70% specific lysis at an effector:target ratio of 10:1 was observed at 5 weeks. IL-7 also triggered development of CD3-CD56+ cells from these immature progenitors (up to 24% and 55% appeared in CD34+HLADR- and CD34+HLADR+ cultures, respectively). Our data suggest that BM stromas are not necessary for NK cell development and that IL-2 remains essential for this lineage development and differentiation.

scholarly journals Deciphering the Immunological Phenomenon of Adaptive Natural Killer (NK) Cells and Cytomegalovirus (CMV)

2020 ◽  
Vol 21 (22) ◽  
pp. 8864
Author(s):  
Samantha Barnes ◽  
Ophelia Schilizzi ◽  
Katherine M. Audsley ◽  
Hannah V. Newnes ◽  
Bree Foley
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Cell Receptor ◽  
Vital Role ◽  
Immune Memory ◽  
Target Cells ◽  
Cytokines And Chemokines ◽  
Adaptive Immune Cells

Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate.

scholarly journals Human natural killer cells can inhibit clonogenic growth of fresh leukemic cells

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 596-599 ◽  
Author(s):  
M Beran ◽  
M Hansson ◽  
R Kiessling
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Colony Growth ◽  
Inhibitory Effect ◽  
Leukemic Cells ◽  
Target Cells ◽  
Human Natural Killer Cells ◽  
Release Assay

Abstract The effect of allogenic human natural killer (NK) cells on fresh leukemic cells from three patients was investigated. The low levels of leukemic target cell lysis in the conventional 51Cr-release assay contrasted with a pronounced inhibitory effect on the colony growth of the clonogeneic leukemic target cells (L-CFC). The ability of allogeneic lymphocytes to inhibit L-CFC increased if they were pretreated with interferon (IFN), which also increased their NK activity, monitored in parallel cytotoxicity assay, against K562. Furthermore, cell separation procedures, based on differences in density among nonadherent lymphocytes, revealed that only NK cell containing fractions were inhibitory. We have also compared the susceptibility to NK-mediated L-CFC inhibition of IFN pretreated leukemic target cells with that of nontreated target cells. As in the case of NK lysis in general, this pretreatment of target cells abolished the presumably NK-mediated L-CFC inhibition. In conclusion, these data provide the first indication that NK cells can inhibit the in vitro growth of fresh clonogenic leukemia cells from patients with nonlymphocytic leukemia. The identity of NK cells as effector is strongly suggested by Percoll separation and responsiveness to interferon; the final proof awaits more sophisticated purification of these cells.

scholarly journals Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell

2020 ◽  
Vol 20 (2) ◽  
pp. 822-832 ◽  
Author(s):  
Wahyu Widowati ◽  
Diana K Jasaputra ◽  
Sutiman B Sumitro ◽  
Mochammad A Widodo ◽  
Tjandrawati Mozef ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Receptor ◽  
Mcf7 Cells ◽  
Activating Receptors ◽  
Tnf Α ◽  
Ifn Γ

Introduction: Breast cancer is one of the leading cause of cancer deaths in women. Metastasis in BC is caused by immuno- surveillance deficiency, such NK cell maturation, low NK activity and decreasing cytotoxicity. This study was performed to improve activating receptors and cytotoxicity of NK cells using interleukins (ILs). Methods: Human recombinant IL-2, -15, and -18 were used to induce NK cells. We measured the activating and inhibiting receptors, proliferation activity of NK cells, and the cytotoxicity of NK cells on BC cells (MCF7). The effects of ILs were tested on the NK cell receptors CD314, CD158a and CD107a with flowcytometry, proliferation at various incubation times with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and concen- trations of TNF-α and IFN-γ by NK cells with ELISA. Results: ILs increased NK cell receptor levels (CD314, CD158a, and CD107a) at 24 hours of incubation. ILs increased NK cell viability, which increased with longer incubation. Moreover, ILs-induced NK cells inhibited proliferation in MCF7 cells, as well as increased TNF-α, IFN-γ, PRF1 and GzmB secretion. Conclusion: IL-2, IL-15, and IL-18 improved activating receptors and proliferation of NK cells. IL-induced NK cells in- creased TNF-α, IFN-γ, PRF1 and GzmB secretion and cytotoxic activity on BC cells. High NK cell numbers increased BC cell growth inhibition. Keywords: Activator; breast cancer; interleukins; natural killer; receptor.

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