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https://www.readbyqxmd.com/read/28529313/impact-of-killer-immunoglobulin-like-receptor-and-human-leukocyte-antigen-genotypes-on-the-efficacy-of-immunotherapy-in-acute-myeloid-leukemia
#1
E Bernson, A Hallner, F E Sander, O Wilsson, O Werlenius, A Rydström, R Kiffin, M Brune, R Foà, J Aurelius, A Martner, K Hellstrand, F B Thorén
Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), i.e. a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28514662/a-murine-intestinal-intraepithelial-nkp46-negative-innate-lymphoid-cell-population-characterized-by-group-1-properties
#2
Aline Van Acker, Konrad Gronke, Aindrila Biswas, Liesbet Martens, Yvan Saeys, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Patrick Matthys, Tom Taghon, Bart Vandekerckhove, Jean Plum, Ildiko Rita Dunay, Andreas Diefenbach, Georges Leclercq
The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα(+) T lymphocytes, and CD49a(+) liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28503177/the-innate-immune-cross-talk-between-nk-cells-and-eosinophils-is-regulated-by-the-interaction-of-natural-cytotoxicity-receptors-with-eosinophil-surface-ligands
#3
Silvia Pesce, Fredrik B Thoren, Claudia Cantoni, Carola Prato, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Previous studies suggested that the cross talk between NK cells and other cell types is crucial for the regulation of both innate and adaptive immune responses. In the present study, we analyzed the phenotypic and functional outcome of the interaction between resting or cytokine-activated NK cells and eosinophils derived from non-atopic donors. Our results provide the first evidence that a natural cytotoxicity receptor (NCR)/NCR ligand-dependent cross talk between NK cells and eosinophils may be important to upregulate the activation state and the effector function of cytokine-primed NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28498408/induction-of-il-17-production-from-human-peripheral-blood-cd4-cells-by-asbestos-exposure
#4
Megumi Maeda, Ying Chen, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Hidenori Matsuzaki, Shoko Yamamoto, Tamayo Hatayama, Miho Ikeda, Yasumitsu Nishimura, Takemi Otsuki
We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28480349/complement-factor-p-is-a-ligand-for-the-natural-killer-cell-activating-receptor-nkp46
#5
Emilie Narni-Mancinelli, Laurent Gauthier, Myriam Baratin, Sophie Guia, Aurore Fenis, Ala-Eddine Deghmane, Benjamin Rossi, Patrick Fourquet, Bertrand Escalière, Yann M Kerdiles, Sophie Ugolini, Muhamed-Kheir Taha, Eric Vivier
Innate lymphoid cells (ILCs) are involved in immune responses to microbes and various stressed cells, such as tumor cells. They include group 1 [such as natural killer (NK) cells and ILC1], group 2, and group 3 ILCs. Besides their capacity to respond to cytokines, ILCs detect their targets through a series of cell surface-activating receptors recognizing microbial and nonmicrobial ligands. The nature of some of these ligands remains unclear, limiting our understanding of ILC biology. We focused on NKp46, which is highly conserved in mammals and expressed by all mature NK cells and subsets of ILC1 and ILC3...
April 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28456791/nk-cells-and-multiple-myeloma-associated-endothelial-cells-molecular-interactions-and-influence-of-il-27
#6
Alessandra Dondero, Beatrice Casu, Francesca Bellora, Angelo Vacca, Annunziata De Luisi, Maria Antonia Frassanito, Claudia Cantoni, Silvia Gaggero, Daniel Olive, Alessandro Moretta, Cristina Bottino, Roberta Castriconi
Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424697/regulation-of-the-functions-of-natural-cytotoxicity-receptors-by-interactions-with-diverse-ligands-and-alterations-in-splice-variant-expression
#7
REVIEW
Tatiana Pazina, Avishai Shemesh, Michael Brusilovsky, Angel Porgador, Kerry S Campbell
The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44, and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have classically been defined as activating receptors that trigger cytotoxicity and cytokine responses by NK cells upon engaging with ligands on tumor cells. Several new findings, however, have challenged this model and identified alternative mechanisms regulating the function of NCRs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28414896/nk-cells-in-self-limited-hcv-infection-exhibit-a-more-extensively-differentiated-but-not-memory-like-repertoire
#8
Rik A de Groen, Zwier M A Groothuismink, Gertine van Oord, Neeltje A Kootstra, Harry L A Janssen, Maria Prins, Janke Schinkel, André Boonstra
Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings...
April 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28410411/hepatitis-c-virus-impairs-natural-killer-cell-activity-via-viral-serine-protease-ns3
#9
Chang Mo Yang, Joo Chun Yoon, Jeon Han Park, Jae Myun Lee
Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection...
2017: PloS One
https://www.readbyqxmd.com/read/28405525/obinutuzumab-mediated-high-affinity-ligation-of-fc%C3%AE-riiia-cd16-primes-nk-cells-for-ifn%C3%AE-production
#10
Cristina Capuano, Chiara Pighi, Rosa Molfetta, Rossella Paolini, Simone Battella, Gabriella Palmieri, Giuseppe Giannini, Francesca Belardinilli, Angela Santoni, Ricciarda Galandrini
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#11
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28396119/interferon-%C3%AE-production-by-tubulointerstitial-human-cd56-bright-natural-killer-cells-contributes-to-renal-fibrosis-and-chronic-kidney-disease-progression
#12
Becker M P Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Melissa J Rist, Kenneth Beagley, Helen Healy, Andrew J Kassianos
Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3(-)CD56(+)) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28372951/disturbances-in-iron-homeostasis-result-in-accelerated-rejection-after-experimental-heart-transplantation
#13
Thomas Resch, Muhammad Imtiaz Ashraf, Paul Viktor Ritschl, Susanne Ebner, Cornelia Fabritius, Andrea Brunner, Georg Schäfer, Heinz Regele, Julia Günther, Günter Weiss, Katja Kotsch
BACKGROUND: Clinical data suggest that iron disturbances deleteriously affect graft survival after heart transplantation (HTx), but immunological mechanisms underlying this phenomenon have not yet been elucidated. METHODS: To identify the mechanistic influence of iron in a murine model of HTx, fully allogeneic BALB/c donor organs were transplanted into iron-overloaded or iron-deficient C57BL/6 mice, and recipients were analyzed for functional and immunological parameters...
March 7, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28328926/frequency-and-role-of-nkp46-and-nkg2a-in-hepatitis-b-virus-infection
#14
Teppei Yoshioka, Tomohide Tatsumi, Takuya Miyagi, Kaori Mukai, Kumiko Nishio, Akira Nishio, Yoshinobu Yokoyama, Takahiro Suda, Tadashi Kegasawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara
BACKGROUND AND AIM: Natural Killer (NK) cells are involved in the control of viral infection. However, the role of NK cells in chronic hepatitis B (CHB) remains unclear. This study investigated the frequencies and roles of NK cells in CHB, with a focus on activating receptor NKp46 and inhibitory receptor NKG2A. PATIENTS/METHOD: Peripheral blood lymphocytes were obtained from 71 CHB patients and 37 healthy subjects (HS). The expressions of NKp46 and NKG2A were analyzed using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28261217/expression-of-nkp46-splice-variants-in-nasal-lavage-following-respiratory-viral-infection-domain-1-negative-isoforms-predominate-and-manifest-higher-activity
#15
Yonat Shemer-Avni, Kiran Kundu, Avishai Shemesh, Michael Brusilovsky, Rami Yossef, Mesfin Meshesha, Semaria Solomon-Alemayehu, Shai Levin, Orly Gershoni-Yahalom, Kerry S Campbell, Angel Porgador
The natural killer (NK) cell activating receptor NKp46/NCR1 plays a critical role in elimination of virus-infected and tumor cells. The NCR1 gene can be transcribed into five different splice variants, but the functional importance and physiological distribution of NKp46 isoforms are not yet fully understood. Here, we shed light on differential expression of NKp46 splice variants in viral respiratory tract infections and their functional difference at the cellular level. NKp46 was the most predominantly expressed natural cytotoxicity receptor in the nasal lavage of patients infected with four respiratory viruses: respiratory syncytia virus, adenovirus, human metapneumovirus, or influenza A...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223394/primary-adrenal-insufficiency-is-associated-with-impaired-natural-killer-cell-function-a-potential-link-to-increased-mortality
#16
Irina Bancos, Jon Hazeldine, Vasileios Chortis, Peter Hampson, Angela E Taylor, Janet M Lord, Wiebke Arlt
OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection...
April 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28197362/prognostic-impact-of-the-expression-of-ncr1-and-ncr3-nk-cell-receptors-and-pd-l1-on-advanced-non-small-cell-lung-cancer
#17
Laetitia Fend, Sylvie Rusakiewicz, Julien Adam, Bérangère Bastien, Anne Caignard, Meriem Messaoudene, Christina Iribarren, Isabelle Cremer, Aurélien Marabelle, Christophe Borg, Michaela Semeraro, Luc Barraud, Jean-Marc Limacher, Alexander Eggermont, Guido Kroemer, Laurence Zitvogel
The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified NCR1 (which codes for NKp46) and NCR3 (which codes for NKp30), as well as that of three NCR3 splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28191644/nk-cell-receptors-nkp46-and-ncr1-control-human-metapneumovirus-infection
#18
Mohammad Diab, Ariella Glasner, Batya Isaacson, Yotam Bar-On, Yaron Drori, Rachel Yamin, Alexandra Duev-Cohen, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Stipan Jonjic, Eran Bacharach, Ofer Mandelboim
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46-activating receptor and its mouse orthologue Ncr1, both members of the natural cytotoxicity receptor (NCR) family, recognized an unknown ligand expressed by HMPV-infected human cells...
February 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28165478/a-distinct-innate-lymphoid-cell-population-regulates-tumor-associated-t-cells
#19
Sarah Q Crome, Linh T Nguyen, Sandra Lopez-Verges, S Y Cindy Yang, Bernard Martin, Jennifer Y Yam, Dylan J Johnson, Jessica Nie, Michael Pniak, Pei Hua Yen, Anca Milea, Ramlogan Sowamber, Sarah Rachel Katz, Marcus Q Bernardini, Blaise A Clarke, Patricia A Shaw, Philipp A Lang, Hal K Berman, Trevor J Pugh, Lewis L Lanier, Pamela S Ohashi
Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56(+)CD3(-) population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production...
March 2017: Nature Medicine
https://www.readbyqxmd.com/read/28154569/regulation-of-nk-cell-activation-and-effector-functions-by-the-il-12-family-of-cytokines-the-case-of-il-27
#20
REVIEW
Norberto Walter Zwirner, Andrea Ziblat
Natural killer (NK) cells are characterized by their ability to detect and induce apoptosis of susceptible target cells and by secretion of immunoregulatory cytokines such as IFN-γ. Activation of these effector functions is triggered upon recognition of tumor and pathogen (mostly virus)-infected cells and because of a bidirectional cross talk that NK cells establish with other cells of myeloid origin such as dendritic cells (DC) and macrophages. A common characteristic of these myeloid cells is their ability to secrete different members of the IL-12 family of cytokines such as IL-12, IL-23, and IL-27 and cytokines such as IL-15 and IL-18...
2017: Frontiers in Immunology
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