scholarly journals A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 174-193
Author(s):  
Jenny Valentina Garmendia ◽  
Juan Bautista De Sanctis
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Inflammatory Cells ◽  
Cell Physiology ◽  
Therapeutic Approaches ◽  
Pharmacological Modulation ◽  
New Therapeutic Approaches ◽  
Pharmacologic Modulation ◽  
Inflammatory Burden

NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

scholarly journals The Advances and Challenges of NK Cell-Based Cancer Immunotherapy

2021 ◽  
Vol 28 (2) ◽  
pp. 1077-1093
Author(s):  
Synat Kang ◽  
Xuefeng Gao ◽  
Li Zhang ◽  
Erna Yang ◽  
Yonghui Li ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Nk Cell ◽  
Tumor Development ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Clinical Applications ◽  
Therapeutic Approaches ◽  
Leukocyte Antigens ◽  
Recognition Specificity

Natural killer (NK) cells can be widely applied for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization or human leukocyte antigens-matching. Several NK-based therapeutic approaches have been attempted in clinical practice, but their efficacy is not sufficient to suppress tumor development mainly because of lacking specificity. To this end, the engineering of NK cells with T cell receptor along with CD3 subunits (TCR-NK) has been developed to increase the reactivity and recognition specificity of NK cells toward tumor cells. Here, we review recent advances in redirecting NK cells for cancer immunotherapy and discuss the major challenges and future explorations for their clinical applications.

scholarly journals NK Cell-Based Immunotherapy and Therapeutic Perspective in Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Changqing Pan ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang ◽  
Wei Zhang
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Primary Brain Tumor ◽  
Therapeutic Approaches ◽  
Independent Manner ◽  
Clinical Prognosis ◽  
Cell Based Therapy ◽  
Current Therapies ◽  
Immunosuppressive Microenvironment ◽  
Therapeutic Perspective

Glioma is the most common malignant primary brain tumor diagnosed in adults. Current therapies are unable to improve its clinical prognosis, imposing the need for innovative therapeutic approaches. The main reason for the poor prognosis is the great cell heterogeneity of the tumor and its immunosuppressive microenvironment. Development of new therapies that avoid this immune evasion could improve the response to the current treatments. Natural killer (NK) cells are an intriguing candidate for the next wave of therapies because of several unique features that they possess. For example, NK cell-based immunotherapy causes minimal graft-versus-host disease. Cytokine release syndrome is less likely to occur during chimeric antigen receptor (CAR)-NK therapy, and CAR-NK cells can kill targets in a CAR-independent manner. However, NK cell-based therapy in treating glioma faces several difficulties. For example, CAR molecules are not sufficiently well designed so that they will thoroughly release functioning NK cells. Compared to hematological malignancies, the application of many potential NK cell-based therapies in glioma lags far behind. Here, we review several issues of NK cells and propose several strategies that will improve the efficacy of NK cell-based cancer immunotherapy in the treatment of glioma.

scholarly journals NK Cells in the Treatment of Hematological Malignancies

2019 ◽  
Vol 8 (10) ◽  
pp. 1557 ◽  
Author(s):  
Gonzalez-Rodriguez ◽  
Villa-Álvarez ◽  
Sordo-Bahamonde ◽  
Lorenzo-Herrero ◽  
Gonzalez
Keyword(s):  
Antitumor Activity ◽  
Nk Cells ◽  
Cancer Cells ◽  
Nk Cell ◽  
Hematologic Malignancies ◽  
Therapeutic Approaches ◽  
Hematopoietic Stem ◽  
Checkpoint Proteins ◽  
Hematological Cancers ◽  
Dependent Cell

: Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases.

Efficient and Reproducible Retroviral Infection of Primary Human Natural Killer Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1348-1348
Author(s):  
Brian Becknell ◽  
Rossana Trotta ◽  
Jianhua Yu ◽  
Wei Ding ◽  
Hsiaoyin C. Mao ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Targeted Delivery ◽  
Magnetic Beads ◽  
Nk Cell ◽  
Human Peripheral Blood ◽  
Cell Physiology ◽  
Gene Products ◽  
Successful Infection

Abstract Molecular characterization of human natural killer (NK) cells will require targeted gene delivery to inhibit and activate specific signaling pathways, yet to our knowledge, an effective means to deliver such products for long-term gene expression without disrupting normal cellular processes has not been described. In this study we have developed a retroviral strategy to effectively express gene products in the NK cell, whereby its effector functions of cytotoxicity and cytokine production remain intact. Using an EBV/retroviral hybrid vector PINCO, we demonstrate infection of human peripheral blood NK cells with simultaneous expression of a marker for infection - the enhanced green fluorescent protein (EGFP) - along with various genes of interest. This technique results in successful infection of the CD56dim NK population that predominates among human peripheral blood NK and is the effector of antibody-dependent cellular cytotoxicity (ADCC) and natural killing. In addition, we demonstrate infection of the CD56bright NK subset as well as the NK-92 and NK-L cell lines. Finally, we modify PINCO to express a cytoplasmically truncated murine CD8 molecule in place of GFP. The resulting vector enables us to transduce NK cells with multiple genes of interest simultaneously and provides an alternative purification method to FACS by using magnetic beads. In summary, we have devised an efficient and highly reproducible methodology for the targeted delivery of gene products to human NK cells that should now provide opportunities to dissect the molecular processes critical to normal NK cell physiology and to genetically manipulate NK cell populations prior to their administration in cancer therapy.

scholarly journals Up-and-down immunity of pregnancy in humans

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1216 ◽  
Author(s):  
Philippe Le Bouteiller ◽  
Armand Bensussan
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Direct Interaction ◽  
Extravillous Trophoblast ◽  
Placental Development ◽  
Local Immunity ◽  
Healthy Pregnancy ◽  
Maternal Immune System ◽  
Decidual Cells

One part of the human placenta in early pregnancy is particularly important for local immunity: the decidua basalis, which is transformed endometrium located at the site of embryo implantation. This placental bed tissue contains both maternal uterine immune cells, including decidual natural killer (NK) cells, the dominant leukocyte population exhibiting a unique phenotype, and fetal extravillous trophoblast which comes into direct contact with maternal decidual cells. To establish a successful placental development and healthy pregnancy outcome, the maternal immune system must tolerate paternal antigens expressed by trophoblast cells yet remain efficient for clearing any local pathogen infection. This review deals mainly with decidual NK cells. A key element, among others, to achieve such dual functions is the direct interaction between activating and inhibitory receptors expressed by decidual NK cells and their specific ligands presented by trophoblast or other decidual cells. Depending whether maternal decidual cells and trophoblast are infected by viruses, the balance between activating and inhibitory receptor signals mediated by decidual NK cell–trophoblast cross-talk results in tolerance (healthy pregnancy) or specific killing (pathogen-infected cells).

scholarly journals Ovarian Stimulation Affects the Population of Mouse Uterine NK Cells at Early Pregnancy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Parvin Dorfeshan ◽  
Mojdeh Salehnia ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Nk Cells ◽  
Ovarian Stimulation ◽  
Nk Cell ◽  
Embryo Implantation ◽  
Control Group ◽  
Tissue Samples ◽  
Serum Gonadotropin ◽  
Human Chorionic Gonadotropin Hormone ◽  
Uterine Nk Cells ◽  
Fertile Male

The aim of this study was to determine the influence of ovarian stimulation on endometrial mouse NK cell population. For superovulation, the female adult NMRI mice were injected i.p. with 10 IU of the pregnant mare serum gonadotropin followed 48 h later by an i.p. injection of 10 IU human chorionic gonadotropin hormone. Ovarian stimulated and nonstimulated mice were mated with fertile male. The presence of vaginal plug proved natural pregnancy, and this day was considered as day one of pregnancy. Tissue samples were prepared from the uterine horn and spleen of both groups of study on 7th day of pregnancy. Serum estradiol-17βand progesterone were measured at the same time. The tissue cryosections were prepared and double stained for CD 161 and CD3 markers, and NK cells population was analyzed. Relative frequency of NK cells was significantly lower in stroma and myometrium in hyperstimulated mice compared with the control group. However, no difference was seen in percentage of NK cells in spleen. The ovarian stimulation influences the proportion of uterine NK cells and may affect the embryo implantation.

scholarly journals Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 461 ◽  
Author(s):  
Barbara Bassani ◽  
Denisa Baci ◽  
Matteo Gallazzi ◽  
Alessandro Poggi ◽  
Antonino Bruno ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Nk Cells ◽  
Natural Killer ◽  
Cancer Progression ◽  
Nk Cell ◽  
Dual Function ◽  
Therapeutic Approaches ◽  
New Findings ◽  
Soluble Hla ◽  
The Impact

. Immune cells, as a consequence of their plasticity, can acquire altered phenotype/functions within the tumor microenvironment (TME). Some of these aberrant functions include attenuation of targeting and killing of tumor cells, tolerogenic/immunosuppressive behavior and acquisition of pro-angiogenic activities. Natural killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. In solid malignancies, tumor-associated NK cells (TANK cells) in peripheral blood and tumor-infiltrating NK (TINK) cells show altered phenotypes and are characterized by either anergy or reduced cytotoxicity. Here, we aim at discussing how NK cells can support tumor progression and how induction of angiogenesis, due to TME stimuli, can be a relevant part on the NK cell-associated tumor supporting activities. We will review and discuss the contribution of the TME in shaping NK cell response favoring cancer progression. We will focus on TME-derived set of factors such as TGF-β, soluble HLA-G, prostaglandin E2, adenosine, extracellular vesicles, and miRNAs, which can exhibit a dual function. On one hand, these factors can suppress NK cell-mediated activities but, on the other hand, they can induce a pro-angiogenic polarization in NK cells. Also, we will analyze the impact on cancer progression of the interaction of NK cells with several TME-associated cells, including macrophages, neutrophils, mast cells, cancer-associated fibroblasts, and endothelial cells. Then, we will discuss the most relevant therapeutic approaches aimed at potentiating/restoring NK cell activities against tumors. Finally, supported by the literature revision and our new findings on NK cell pro-angiogenic activities, we uphold NK cells to a key host cellular paradigm in controlling tumor progression and angiogenesis; thus, we should bear in mind NK cells like a TME-associated target for anti-tumor therapeutic approaches.

Natural killer cells and cancer therapy, what we know and where we are going

Immunotherapy ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 1231-1251 ◽  
Author(s):  
Faezeh Ghaemdoust ◽  
Mahsa Keshavarz-Fathi ◽  
Nima Rezaei
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
The Body ◽  
Innate Immune ◽  
Regulatory Function ◽  
Therapeutic Approaches ◽  
Cell Immunotherapy ◽  
And Function ◽  
Cancer Immunosurveillance

Natural killer (NK) cells are among the significant components of innate immune system and they have come to the first line of defense against tumor cells developing inside the body. CD56lo/CD16+NK cells are highly cytotoxic and CD56hi NK cells can produce cytokines and perform a regulatory function. Specific features of NK cells have made them a unique choice for cancer immunotherapy. Simple interventions like cytokine-injection to boost the internal NK cells were the first trials to target these cells. Nowadays, many other types of intervention are under investigation, such as adoptive NK cell immunotherapy. In this paper, we will discuss the biology and function of NK cells in cancer immunosurveillance and therapeutic approaches against cancer via using NK cells.

scholarly journals Immune Circuits to Shape Natural Killer Cells in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3225
Author(s):  
Irene Mattiola
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Antitumor Immunity ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Tumor Escape ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
Cancer Immunity ◽  
Anti Cancer

Natural killer (NK) cells are innate lymphoid cells playing an important role in anti-cancer immunity. NK cells are efficient in controlling the spreading of metastasis but are not very powerful in fighting against primary tumors. The NK cell capability to infiltrate and persist in the tumor microenvironment and to exert their antitumoral functions is often limited by tumor escape mechanisms. These tumor-mediated strategies not only induce NK cell tolerance but also interfere with the NK cell-dependent immune networking. This review will provide an overview of the tumor escape mechanisms impacting NK cells, identify the immune circuits regulating the NK cell-dependent antitumor immunity and revise the emerging therapeutic approaches to unleash NK cells in cancer.

scholarly journals NK Cell-Based Glioblastoma Immunotherapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 522 ◽  
Author(s):  
Irene Golán ◽  
Laura Rodríguez de la Fuente ◽  
Jose Costoya
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
High Capacity ◽  
Primary Brain Tumor ◽  
Therapeutic Approaches ◽  
Current Therapies ◽  
Cellular Components

Glioblastoma (GB) is the most aggressive and most common malignant primary brain tumor diagnosed in adults. GB shows a poor prognosis and, unfortunately, current therapies are unable to improve its clinical outcome, imposing the need for innovative therapeutic approaches. The main reason for the poor prognosis is the great cell heterogeneity of the tumor mass and its high capacity for invading healthy tissues. Moreover, the glioblastoma microenvironment is capable of suppressing the action of the immune system through several mechanisms such as recruitment of cell modulators. Development of new therapies that avoid this immune evasion could improve the response to the current treatments for this pathology. Natural Killer (NK) cells are cellular components of the immune system more difficult to deceive by tumor cells and with greater cytotoxic activity. Their use in immunotherapy gains strength because they are a less toxic alternative to existing therapy, but the current research focuses on mimicking the NK attack strategy. Here, we summarize the most recent studies regarding molecular mechanisms involved in the GB and immune cells interaction and highlight the relevance of NK cells in the new therapeutic challenges.

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