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https://www.readbyqxmd.com/read/30086799/a-possible-new-pathway-in-natural-killer-cell-activation-also-reveals-the-difficulty-in-determining-human-nk-cell-function-in-cancer
#1
Robert J Canter, William J Murphy
Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers...
August 7, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30055825/altered-distribution-and-function-of-splenic-innate-lymphoid-cells-in-adult-chronic-immune-thrombocytopenia
#2
Sylvain Audia, Thomas Moulinet, Marion Ciudad-Bonté, Maxime Samson, Olivier Facy, Pablo Ortega-Deballon, Philippe Saas, Bernard Bonnotte
Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constituted of NKp44- cells...
July 23, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/30008723/-in-vitro-exposure-to-prostratin-but-not-bryostatin-1-improves-natural-killer-cell-functions-including-killing-of-cd4-t-cells-harboring-reactivated-human-immunodeficiency-virus
#3
Maria Giovanna Desimio, Erica Giuliani, Angelo Salvatore Ferraro, Gaspare Adorno, Margherita Doria
In the attempt of purging the HIV-1 reservoir through the "shock-and-kill" strategy, it is important to select latency-reversing agents (LRAs) devoid of deleterious effects on the antiviral function of immune effector cells. Here, we investigated two LRAs with PKC agonist activity, prostratin (PRO) and bryostatin-1 (BRY), for their impact on the function of natural killer (NK) cells, the major effectors of innate immunity whose potential in HIV-1 eradication has emerged in recent clinical trials. Using NK cells of healthy donors, we found that exposure to either PRO or BRY potently activated NK cells, resulting in upmodulation of NKG2D and NKp44 activating receptors and matrix metalloprotease-mediated shedding of CD16 receptor...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29897565/effector-%C3%AE-%C3%AE-t-cells-in-human-renal-fibrosis-and-chronic-kidney-disease
#4
Becker Meng-Po Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Kenneth Beagley, Helen Healy, Andrew J Kassianos
Background: γδ T cells are effector lymphocytes recognized as key players during chronic inflammatory processes. Mouse studies suggest a pathological role for γδ T cells in models of kidney disease. Here we evaluated γδ T cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Methods: γδ T cells were extracted from human kidney tissue and enumerated and phenotyped by multicolour flow cytometry...
April 20, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29875773/nkp44-derived-peptide-binds-proliferating-cell-nuclear-antigen-and-mediates-tumor-cell-death
#5
Avishai Shemesh, Kiran Kundu, Refael Peleg, Rami Yossef, Irena Kaplanov, Susmita Ghosh, Yana Khrapunsky, Orly Gershoni-Yahalom, Tatiana Rabinski, Adelheid Cerwenka, Roee Atlas, Angel Porgador
Proliferating cell nuclear antigen (PCNA) is considered as a hub protein and is a key regulator of DNA replication, repair, cell cycle control, and apoptosis. PCNA is overexpressed in many cancer types, and PCNA overexpression is correlated with cancer virulence. Membrane-associated PCNA is a ligand for the NKp44 (NCR2) innate immune receptor. The purpose of this study was to characterize the PCNA-binding site within NKp44. We have identified NKp44-derived linear peptide (pep8), which can specifically interact with PCNA and partly block the NKp44-PCNA interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740448/working-in-nk-mode-natural-killer-group-2-member-d-and-natural-cytotoxicity-receptors-in-stress-surveillance-by-%C3%AE-%C3%AE-t-cells
#6
REVIEW
Bruno Silva-Santos, Jessica Strid
Natural killer cell receptors (NKRs) are germline-encoded transmembrane proteins that regulate the activation and homeostasis of NK cells as well as other lymphocytes. For γδ T cells, NKRs play critical roles in discriminating stressed (transformed or infected) cells from their healthy counterparts, as proposed in the "lymphoid stress-surveillance" theory. Whereas the main physiologic role is seemingly fulfilled by natural killer group 2 member D, constitutively expressed by γδ T cells, enhancement of their therapeutic potential may rely on natural cytotoxicity receptors (NCRs), like NKp30 or NKp44, that can be induced selectively on human Vδ1+ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29683419/haemagglutinin-neuraminidase-from-hpiv3-mediates-human-nk-regulation-of-t-cell-proliferation-via-nkp44-and-nkp46
#7
Samantha McQuaid, Sinead Loughran, Patrick Power, Paula Maguire, Dermot Walls, Maria Grazia Cusi, Claes Orvell, Patricia Johnson
HPIV3 is a respiratory virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. Currently there is no effective vaccine or anti-viral therapy for this virus. Studies have suggested that poor T cell proliferation following HPIV3 infection is responsible for impaired immunological memory associated with this virus. We have previously demonstrated that NK cells mediate regulation of T cell proliferation during HPIV3 infection. Here we add to these studies by demonstrating that the regulation of T cell proliferation during HPIV3 infection is mediated via NK receptors NKp44 and NKp46 and involves the surface glycoprotein haemagglutinin-neuraminidase but not the fusion protein of the virus...
June 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29650045/characterization-of-the-interaction-between-human-decidua-parietalis-mesenchymal-stem-stromal-cells-and-natural-killer-cells
#8
M H Abumaree, E Bahattab, A Alsadoun, A Al Dosaimani, F M Abomaray, T Khatlani, B Kalionis, M F El-Muzaini, A O Alawad, A S AlAskar
BACKGROUND: Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities. METHODS: DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood...
April 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29580037/analysis-of-the-expression-of-surface-receptors-on-nk-cells-and-nkg2d-on-immunocytes-in-peripheral-blood-of-patients-with-nasopharyngeal-carcinoma
#9
Yuanji Xu, Rui Zhou, Chuanzhong Huang, Mingwei Zhang, Jieyu Li, Jingfeng Zong, Sufang Qiu, Shaojun Lin, Honglin Chen, Yunbin Ye, Jianji Pan
Background: The aberrant expression of surface receptors on immunocytes may represent potential markers of tumor escape for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the expression of representative receptors on natural killer (NK) cells and NK group 2, member D (NKG2D) on immunocytes in the peripheral blood of patients with NPC. Methods: Patients (n = 64) with NPC prior to initiation of treatment were defined as the study group. Healthy volunteers (n = 31) served as the control group...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29542132/how-do-we-manufacture-clinical-grade-interleukin-15-stimulated-natural-killer-cell-products-for-cancer-treatment
#10
Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
June 2018: Transfusion
https://www.readbyqxmd.com/read/29478770/natural-killer-cells-detect-a-tumor-produced-growth-factor-a-vestige-of-antiviral-resistance
#11
Giorgio Trinchieri
In addition to exogenous ligands derived from pathogens, natural killer (NK) and other innate cells can recognize endogenous ligands that often act as markers of stress or damage. A recent study reports that one of these receptors, human NKp44, recognizes PDGF-DD, providing a rare example of the recognition of a soluble growth factor as a stress signal. The recognition of PDGF-DD induces the secretion of cytokines with antitumor activity.
May 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29447242/a-novel-ligand-on-astrocytes-interacts-with-natural-cytotoxicity-receptor-nkp44-regulating-immune-response-mediated-by-nk-cells
#12
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
https://www.readbyqxmd.com/read/29299659/ex-vivo-expanded-nk-cells-from-blood-and-ascites-of-ovarian-cancer-patients-are-cytotoxic-against-autologous-primary-ovarian-cancer-cells
#13
Tina Nham, Sophie M Poznanski, Isabella Y Fan, Mira M Shenouda, Marianne V Chew, Amanda J Lee, Fatemeh Vahedi, Yalda Karimi, Martin Butcher, Dean A Lee, Hal Hirte, Ali A Ashkar
Ovarian cancer (OC) is the leading cause of gynecological cancer-related death in North America. Most ovarian cancer patients (OCPs) experience disease recurrence after first-line surgery and chemotherapy; thus, there is a need for novel second-line treatments to improve the prognosis of OC. Although peripheral blood-derived NK cells are known for their ability to spontaneously lyse tumour cells without prior sensitization, ascites-derived NK cells (ascites-NK cells) isolated from OCPs exhibit inhibitory phenotypes, impaired cytotoxicity and may play a pro-tumourigenic role in cancer progression...
April 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29275861/natural-killer-cells-control-tumor-growth-by-sensing-a-growth-factor
#14
Alexander D Barrow, Melissa A Edeling, Vladimir Trifonov, Jingqin Luo, Piyush Goyal, Benjamin Bohl, Jennifer K Bando, Albert H Kim, John Walker, Mary Andahazy, Mattia Bugatti, Laura Melocchi, William Vermi, Daved H Fremont, Sarah Cox, Marina Cella, Christian Schmedt, Marco Colonna
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest...
January 25, 2018: Cell
https://www.readbyqxmd.com/read/29261670/human-intrahepatic-ilc2-are-il-13positive-amphiregulinpositive-and-their-frequency-correlates-with-model-of-end-stage-liver-disease-score
#15
Hannah C Jeffery, Patrick McDowell, Philipp Lutz, Rebecca E Wawman, Sheree Roberts, Chris Bagnall, Jane Birtwistle, David H Adams, Ye Htun Oo
INTRODUCTION: Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. METHODS: Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function...
2017: PloS One
https://www.readbyqxmd.com/read/29247708/modulation-the-expression-of-natural-killer-cell-activating-receptor-nkp44-in-the-peripheral-blood-of-diffuse-large-b-cell-lymphoma-patients-and-the-correlation-with-clinic-pathological-features
#16
Enas Said Essa, Gehan Abd-Elfatah Tawfeek, Suzan Ahmed El Hassanin, Khloud Gamal Mohammed Emara
NK cell activation is one strategy to improve the immunotherapy of non-Hodgkin's lymphoma. So, we aimed to investigate expression of Natural killer cell activating receptor NKp44 in patients with diffuse large B-cell lymphoma (DLBCL) and its correlation with clinic pathological data. In this study, 30 new cases with DLBCL in addition to 20 healthy control were involved. All were submitted to full history, clinical examination, histopathology, Routine laboratory investigations including CBC, LDH, β2microgloubine and bone marrow examination...
March 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-natural-killer-and-t-cells-differential-surface-expression-of-killer-cell-immunoglobulin-like-receptors
#17
Ariel Podhorzer, Andrés Machicote, Santiago Belén, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood natural killer (NK), natural killer T (NKT) and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activation marker NKp44...
June 2018: Immunology
https://www.readbyqxmd.com/read/29163547/natural-killer-cells-from-the-subcutaneous-adipose-tissue-underexpress-the-nkp30-and-nkp44-in-obese-persons-and-are-less-active-against-major-histocompatibility-complex-class-i-non-expressing-neoplastic-cells
#18
Alireza Shoae-Hassani, Maryam Behfar, Seyed Abdolreza Mortazavi-Tabatabaei, Jafar Ai, Rashin Mohseni, Amir Ali Hamidieh
There are many types of leukocytes reside in subcutaneous adipose tissue (SAT), and among them, natural killer cells (NKs) comprise a major part. We show that the NKs that reside in the SAT (adipose tissue-derived NK cells; ADNKs) of the abdominal region found with phenotypic differences from the NKs circulating in the peripheral blood derived NK cells (PBNKs). In this survey, flow cytometry phenotyping was used to study the differences between the natural cytotoxicity receptor expression on ADNKs and PBNKs of both obese and lean persons...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29089040/veritable-antiviral-capacity-of-natural-killer-cells-in-chronic-hbv-infection-an-argument-for-an-earlier-anti-virus-treatment
#19
Xiaoyan Li, Liang Zhou, Lin Gu, Yurong Gu, Lubiao Chen, Yifan Lian, Yuehua Huang
BACKGROUND: There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. METHODS: A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines...
October 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29045847/cross-tissue-transcriptomic-analysis-of-human-secondary-lymphoid-organ-residing-ilc3s-reveals-a-quiescent-state-in-the-absence-of-inflammation
#20
Yotam E Bar-Ephraim, Ferry Cornelissen, Natalie Papazian, Tanja Konijn, Remco M Hoogenboezem, Mathijs A Sanders, Bart A Westerman, Mehmet Gönültas, Jaap Kwekkeboom, Joke M M Den Haan, Rogier M Reijmers, Reina E Mebius, Tom Cupedo
A substantial number of human and mouse group 3 innate lymphoid cells (ILC3s) reside in secondary lymphoid organs, yet the phenotype and function of these ILC3s is incompletely understood. Here, we employed an unbiased cross-tissue transcriptomic approach to compare human ILC3s from non-inflamed lymph nodes and spleen to their phenotypic counterparts in inflamed tonsils and from circulation. These analyses revealed that, in the absence of inflammation, lymphoid organ-residing ILC3s lack transcription of cytokines associated with classical ILC3 functions...
October 17, 2017: Cell Reports
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