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Natural Killer Cell

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https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#1
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28920951/srebp-controlled-glucose-metabolism-is-essential-for-nk-cell-functional-responses
#2
Nadine Assmann, Katie L O'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate-malate shuttle...
September 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28920584/liver-resident-nk-cells-and-their-potential-functions
#3
Hui Peng, Rui Sun
Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells...
September 18, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28920003/cd226-natural-killer-cells-fail-to-establish-stable-contacts-with-cancer-cells-and-show-impaired-control-of-tumor-metastasis-in-vivo
#4
Ji Sung Kim, Bo Ram Shin, Hong Kyung Lee, Jae Hee Lee, Ki Hun Kim, Jeong Eun Choi, A Young Ji, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
CD226 is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon binding to its ligands expressed on target cells, CD226 activates intracellular signaling that triggers cytokine production and degranulation in NK cells. However, the role of CD226 in contact dynamics between NK and cancer cells has remained unclear. Our time-lapse images showed that individual wild-type CD226(+) NK cells contacted B16F10 melanoma cells for 23.7 min, but Cd226(-/-) NK cells only for 12...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#5
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919994/effect-of-entinostat-on-nk-cell-mediated-cytotoxicity-against-osteosarcoma-cells-and-osteosarcoma-lung-metastasis
#6
Simin Kiany, Gangxiong Huang, Eugenie S Kleinerman
There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell lysis and increases the efficacy of NK cell therapy for OS lung metastasis. Entinostat upregulated ligands for NK cell-activating receptors (major histocompatibility complex [MHC] class I polypeptide-related chain A [MICA] and B [MICB]; UL16 binding proteins 1, 2, 5, and 6; and CD155) on OS cells both in vitro and in vivo and led to more susceptibility to NK cell-mediated cytotoxicity in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919991/umbilical-cord-blood-cd34-progenitor-derived-nk-cells-efficiently-kill-ovarian-cancer-spheroids-and-intraperitoneal-tumors-in-nod-scid-il2rg-null-mice
#7
Janneke S Hoogstad-van Evert, Jeannette Cany, Dirk van den Brand, Manon Oudenampsen, Roland Brock, Ruurd Torensma, Ruud L Bekkers, Joop H Jansen, Leon F Massuger, Harry Dolstra
Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919894/potentiation-of-natural-killer-cells-for-cancer-immunotherapy-a-review-of-literature
#8
REVIEW
Lacy E Lowry, William A Zehring
It is widely acknowledged that the human immune system plays a crucial role in preventing the formation and progression of innumerable types of cancer (1). The mechanisms by which this occurs are numerous, including contributions from both the innate and adaptive immune systems. As such, immunotherapy has long been believed to be an auspicious solution in the treatment of malignancy (2). Recent research has highlighted the promise of natural killer (NK) cells as a more directed immunotherapy approach. This paper will focus on the methods of potentiation of NK cells for their use in cancer therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919377/combination-cancer-therapy-using-chimeric-antigen-receptor-engineered-natural-killer-cells-as-drug-carriers
#9
Elizabeth L Siegler, Yu Jeong Kim, Xianhui Chen, Natnaree Siriwon, John Mac, Jennifer A Rohrs, Paul D Bryson, Pin Wang
The therapeutic limitations of conventional chemotherapeutic drugs include chemo-resistance, tumor recurrence, and metastasis. Numerous nanoparticle-based active targeting approaches have emerged to enhance the intracellular concentration of drugs in tumor cells; however, efficient delivery of these systems to the tumor site while sparing healthy tissue remains elusive. Recently, much attention has been given to human immune-cell-directed nanoparticle drug delivery, because immune cells can traffic to the tumor and inflammatory sites...
August 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#10
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28916719/kir2ds2-recognizes-conserved-peptides-derived-from-viral-helicases-in-the-context-of-hla-c
#11
Mohammed M Naiyer, Sorcha A Cassidy, Andrea Magri, Vanessa Cowton, Kevin Chen, Salah Mansour, Hariklia Kranidioti, Berenice Mbirbindi, Pauline Rettman, Scott Harris, Liam J Fanning, Arend Mulder, Franz H J Claas, Andrew D Davidson, Arvind H Patel, Marco A Purbhoo, Salim I Khakoo
Killer cell immunoglobulin-like receptors (KIRs) are rapidly evolving species-specific natural killer (NK) cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of major histocompatibility complex class I. We started by documenting that peptide LNPSVAATL from the hepatitis C virus (HCV) helicase binds HLA-C*0102, leading to NK cell activation through engagement of KIR2DS2...
September 15, 2017: Science Immunology
https://www.readbyqxmd.com/read/28916655/tethering-il2-to-its-receptor-il2r%C3%AE-enhances-anti-tumor-activity-and-expansion-of-natural-killer-nk92-cells
#12
Youssef Jounaidi, Joseph F Cotten, Keith W Miller, Stuart A Forman
Interleukin-2 (IL2) is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ and IL2Rγ...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916644/subset-and-tissue-defined-stat5-thresholds-control-homeostasis-and-function-of-innate-lymphoid-cells
#13
Alejandro V Villarino, Giuseppe Sciumè, Fred P Davis, Shigeru Iwata, Beatrice Zitti, Gertraud W Robinson, Lothar Hennighausen, Yuka Kanno, John J O'Shea
Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15...
September 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28915900/a-randomized-phase-ii-study-to-assess-the-effect-of-adjuvant-immunotherapy-using-%C3%AE-galcer-pulsed-dendritic-cells-in-the-patients-with-completely-resected-stage-ii-iiia-non-small-cell-lung-cancer-study-protocol-for-a-randomized-controlled-trial
#14
Hideo Saka, Chiyoe Kitagawa, Yukito Ichinose, Mitsuhiro Takenoyama, Hidenori Ibata, Tatsuo Kato, Koji Takami, Motohiro Yamashita, Tadashi Maeda, Sadanori Takeo, Hitoshi Ueda, Kan Okabayashi, Seiji Nagashima, Tadayuki Oka, Hidenori Kouso, Seiichi Fukuyama, Kentaro Yoshimoto, Mototsugu Shimokawa, Akiko M Saito, Suminobu Ito
BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only)...
September 15, 2017: Trials
https://www.readbyqxmd.com/read/28915651/programmed-differentiated-natural-killer-cells-kill-leukemia-cells-by-engaging-slam-family-receptors
#15
Yang Wu, Young Li, Binqing Fu, Linlin Jin, Xiaohu Zheng, Aimei Zhang, Rui Sun, Zhigang Tian, Haiming Wei
Natural killer (NK) cells are important innate immune cells that can directly kill transformed or virus-infected cells. The adoptive transfer of NK cells has been used to treat hematological malignancies; however, the limited sources and quantities of NK cells have restricted their clinical application. Here, we acquired sufficient quantities of functional NK cells from CD34(+) cells treated with a cytokine cocktail. Microarray analysis of the cultured cells revealed a two-stage pattern of programmed differentiation during NK cell development...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#16
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915450/molecular-signature-and-functional-analysis-of-uterine-ilcs-in-mouse-pregnancy
#17
Minmin Li, Yimin Gao, Liang Yong, Dake Huang, Jijia Shen, Miao Liu, Cuiping Ren, Xin Hou
In addition to natural killer cells, other innate lymphoid cells have recently been identified in the mouse and human uterus, but their roles in successful pregnancy remain poorly defined. In this study, we examined the dynamic changes of uterine innate lymphoid cells throughout pregnancy in mice. We found that the total number of uterine innate lymphoid cells markedly increased at early-gestation. Among the three groups of uterine innate lymphoid cells, the number of the group 2 uterine innate lymphoid cells increased the most during pregnancy...
September 8, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28915405/hepatic-immunopathology-during-occult-hepacivirus-re-infection
#18
Cordelia Manickam, Amanda J Martinot, Rhianna A Jones, Valerie Varner, R Keith Reeves
Despite drug advances for Hepatitis C virus (HCV), re-infections remain prevalent in high-risk populations. Unfortunately, the role of preexisting viral immunity and how it modulates re-infection is unclear. GBV-B infection of common marmosets is a useful model to study tissue immune responses in hepacivirus infections, and in this study we re-challenged 4 animals after clearance of primary viremia. Although only low-to-absent viremia was observed following re-challenge, GBV-B viral RNA was detectable in liver, confirming re-infection...
September 12, 2017: Virology
https://www.readbyqxmd.com/read/28913994/mouse-model-of-il-17-dominant-rhinitis-using-polyinosinic-polycytidylic-acid
#19
Jun Sang Bae, Eun Hee Kim, Ji Hye Kim, Ji Hun Mo
Interleukin (IL)-17 plays an important role in rhinitis and the level thereof correlates with the severity of disease. However, no mouse model for IL-17-dominant rhinitis has yet been developed. Our objective was to establish a mouse model of IL-17-dominant rhinitis via intranasal application of polyinosinic-polycytidylic acid (abbreviated as Poly(I:C)). Mice were divided into 6 groups (n=8 for each group); 1) 1 negative control group, 2) 1 positive control group (OVA/alum model), 3) 2 Poly(I:C) groups (10 or 100 μg), and 4) 2 OVA/Poly(I:C) groups (10 or 100 μg)...
November 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28912779/v%C3%AE-4-%C3%AE-%C3%AE-t-cells-aggravate-severe-h1n1-influenza-virus-infection-induced-acute-pulmonary-immunopathological-injury-via-secreting-interleukin-17a
#20
Chunxue Xue, Mingjie Wen, Linlin Bao, Hui Li, Fengdi Li, Meng Liu, Qi Lv, Yunqing An, Xulong Zhang, Bin Cao
The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown...
2017: Frontiers in Immunology
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