scholarly journals Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Esraa Elaraby ◽  
Abdullah Imadeddin Malek ◽  
Hanan W. Abdullah ◽  
Noha Mousaad Elemam ◽  
Maha Saber-Ayad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Innate Immune System ◽  
Killer Cell ◽  
Innate Immune ◽  
Obese Patients ◽  
Cell Dysfunction

Natural killer cells (NK cells) are a crucial constituent of the innate immune system as they mediate immunity against viruses, bacteria, parasites, and most importantly, tumor cells. The exact mechanism of how the innate immune system and specifically NK cells interact with cancer cells is complex and is yet to be understood. Several factors that constitute the tumor microenvironment (TME) such as hypoxia and TGF-β are believed to play a role in the complex physiological reaction of NK cells to tumor cells. On the other hand, several risk factors are implicated in the development and progression of breast cancer, most importantly: obesity. Cytokines released from adipose tissue such as adipokines, leptin, and resistin, among others, are also believed to facilitate tumor progression. In this study, we aimed to build a triad of breast cancer, obesity, and NK cell dysfunction to elucidate a link between these pillars on a cellular level. Directing efforts towards solidifying the link between these factors will help in designing a targeted immunotherapy with a low side-effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.

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.

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

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 O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride enhances influx of effective NK and NKT cells in murine breast cancer

2020 ◽  
Vol 77 (7) ◽  
pp. 715-723
Author(s):  
Milena Jurisevic ◽  
Nikola Jagic ◽  
Nevena Gajovic ◽  
Aleksandar Arsenijevic ◽  
Milan Jovanovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Tumor Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Fas Ligand ◽  
Killer Cell ◽  
Nkt Cells ◽  
Tumor Cell Death

Background/Aim. O,O'-diethyl-(S,S)-ethylenediamine- N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride (DEEDCP) has been found to possess promising cytotoxic activity against various tumor cell lines. Also, DE-EDCP reduces tumor progression by several mechanisms such as triggering tumor cell death and inhibition of cell proliferation. The aim of present study was to further evaluate antitumor activity of DE-EDCP by investigating effects on migratory potential of tumor cells and anti-tumor immune response. Methods. Migratory potential of DE-EDCP was evaluated by scratch wound assay. Female BALB/c mice were inoculated with 4T1 breast cancer cells and treatment with DE-EDCP started five days following orthotopic tumor implantation. The frequency and phenotype of tumorinfiltrating natural killer (NK) and natural killer T (NKT) cells were analyzed by flow cytometry. Results. DE-EDCP inhibited migratory potential of highly metastatic 4T1 cells. DE-EDCP facilitated accumulation of CD3+CD49+ NKT cells and CD3-CD49+ NK cells in tumor microenvironment. DE-EDCP treatment led to significant decrement of tumor infiltrating anergic NKT cells expressing cytotoxic Tlymphocyte- associated protein 4 (CTLA-4), killer cell lectin like receptor G1 (KLRG-1) and programmed cell death protein- 1 (PD-1). Mice given DE-EDCP had significantly increased percentages of tumoricidal fas ligand (FasL) positive NK cells. Conclusion. DE-EDCP inhibits murine breast cancer progression through direct effects on tumor cells and by facilitating anti-tumor immunity. DE-EDCP enhances accumulation, promotes tumoricidal phenotype and maintenances responsiveness of NK and NKT cells in 4T1 murine breast cancer.

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.

The Innate Immune System and Cardiovascular Disease in ESKD: Monocytes and Natural Killer Cells

2020 ◽  
Vol 19 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Evangelia Dounousi ◽  
Anila Duni ◽  
Katerina K. Naka ◽  
Georgios Vartholomatos ◽  
Carmine Zoccali
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Immune System ◽  
Kidney Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Innate Immune System ◽  
Nkt Cells ◽  
Innate Immune ◽  
Monocyte Subsets

Adverse innate immune responses have been implicated in several disease processes, including cardiovascular disease (CVD) and chronic kidney disease (CKD). The monocyte subsets natural killer (NK) cells and natural killer T (NKT) cells are involved in innate immunity. Monocytes subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure. Upregulated activity and counts of proinflammatory CD16+ monocyte subsets are associated with clinical indices of atherosclerosis, heart failure syndromes and CKD. Advanced CKD is a complex state of persistent systemic inflammation characterized by elevated expression of proinflammatory and pro-atherogenic CD14++CD16+ monocytes, which are associated with cardiovascular events and death both in the general population and among patients with CKD. Diminished NK cells and NKT cells counts and aberrant activity are observed in both coronary artery disease and end-stage kidney disease. However, evidence of the roles of NK cells and NKT cells in atherogenesis in advanced CKD is circumstantial and remains to be clarified. This review describes the available evidence regarding the roles of specific immune cell subsets in the pathogenesis of CVD in patients with CKD. Future research is expected to further uncover the links between CKD associated innate immune system dysregulation and accelerated CVD and will ideally be translated into therapeutic targets.

Mesenchymal Stromal Cells and Natural Killer Cells: A Complex Story of Love and Hate

2019 ◽  
Vol 14 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Mehdi Najar ◽  
Mohammad Fayyad-Kazan ◽  
Makram Merimi ◽  
Arsène Burny ◽  
Dominique Bron ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Complex Interactions ◽  
Cell Based Therapy

Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation potential and potent immunomodulatory capacity, represent a promising, safe and powerful cell based-therapy for repairing tissue damage and/or treating diseases associated with aberrant immune responses. Natural killer (NK) cells are granular lymphocytes of the innate immune system that function alone or in combination with other immune cells to combat both tumors and virally infected cells. After their infusion, MSCs are guided by host inflammatory elements and can interact with different immune cells, particularly those of the innate immune system. Although some breakthroughs have been achieved in understanding these interactions, much remains to be determined. In this review, we discuss the complex interactions between NK cells and MSCs, particularly the importance of improving the therapeutic value of MSCs.

scholarly journals Natural Killer Cells Determine Development of Allergen-induced Eosinophilic Airway Inflammation in Mice

1999 ◽  
Vol 189 (3) ◽  
pp. 553-562 ◽  
Author(s):  
Magnus Korsgren ◽  
Carl G.A. Persson ◽  
Frank Sundler ◽  
Torbjörn Bjerke ◽  
Tony Hansson ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Innate Immune System ◽  
Airway Disease ◽  
Nkt Cells ◽  
Innate Immune ◽  
Tissue Eosinophilia

The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1+ T cells (NKT cells), and γ/δ T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1+ cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3+ T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon γ–producing splenic cells were diminished in mice depleted of NK1.1+ cells before the priming regime. Depletion of NK1.1+ cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in γ/δ T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

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 The Potential for Cancer Immunotherapy in Targeting Surgery-Induced Natural Killer Cell Dysfunction

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Marisa Market ◽  
Katherine Baxter ◽  
Leonard Angka ◽  
Michael Kennedy ◽  
Rebecca Auer
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Clonal Selection ◽  
Killer Cell ◽  
Cancer Recurrence ◽  
Effector Functions ◽  
Cell Dysfunction ◽  
Cell Functions

Natural Killer (NK) cells are granular lymphocytes of the innate immune system that are able to recognize and kill tumor cells without undergoing clonal selection. Discovered over 40 years ago, they have since been recognized to possess both cytotoxic and cytokine-producing effector functions. Following trauma, NK cells are suppressed and their effector functions are impaired. This is especially important for cancer patients undergoing the removal of solid tumors, as surgery has shown to contribute to the development of metastasis and cancer recurrence postoperatively. We have recently shown that NK cells are critical mediators in the formation of metastasis after surgery. While research into the mechanism(s) responsible for NK cell dysfunction is ongoing, knowledge of these mechanisms will pave the way for perioperative therapeutics with the potential to improve cancer outcomes by reversing NK cell dysfunction. This review will discuss mechanisms of suppression in the postoperative environment, including hypercoagulability, suppressive soluble factors, the expansion of suppressive cell populations, and how this affects NK cell biology, including modulation of cell surface receptors, the potential for anergy, and immunosuppressive NK cell functions. This review will also outline potential immunotherapies to reverse postoperative NK dysfunction, with the goal of preventing surgery-induced metastasis.

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