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Lazar Vujanovic, Christopher Chuckran, Yan Lin, Fei Ding, Cindy A Sander, Patricia M Santos, Joel Lohr, Afshin Mashadi-Hossein, Sarah Warren, Andy White, Alan Huang, John M Kirkwood, Lisa H Butterfield
Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients...
2019: Frontiers in Immunology
Allistair A Abraham, Haili Lang, Emily Riehm Meier, Robert S Nickel, Marcus Dean, Nurah Lawal, Barbara Speller-Brown, Yunfei Wang, Leslie Kean, Catherine M Bollard
BACKGROUND: Sickle cell disease (SCD) is increasingly recognized as a red blood cell disorder modulated by abnormally increased inflammation. We have previously shown that in patients with SCD not on a disease-modifying therapy (hydroxyurea or chronic transfusions), natural killer (NK) cell numbers are increased. In the current study, we further investigated the NK cell function to determine if there was evidence of increased activation and cytotoxicity. PROCEDURE: We conducted a cross-sectional study of 44 patients with HbSS/HbSβ0 thalassemia at steady state (hydroxyurea = 13, chronic transfusion = 11, no disease-modifying therapy = 20) and 23 healthy controls...
January 4, 2019: Pediatric Blood & Cancer
Qin Huang, Jinli Ding, Meng Gong, Min Wei, Qinghong Zhao, Jing Yang
AIM: Natural killer (NK) cells, as key regulatory cells, accumulate at the maternal-fetal interface in large numbers. This study explored the effect of miR-30e on regulating the activity and function of peripheral blood NK cells (PB-NK cells) and decidua NK cells (D-NK cells) by targeting PRF1 in immune tolerance of maternal-fetal interface. METHODS: Expressions of miR-30e in PB and decidua tissues from 49 patients with recurrent spontaneous abortion and 52 normal pregnant women were measured using PCR...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anna Maria Trotta, Sara Santagata, Serena Zanotta, Crescenzo D'Alterio, Maria Napolitano, Giuseppina Rea, Rosa Camerlingo, Fabio Esposito, Elvira Lamantia, Annamaria Anniciello, Giovanni Botti, Nicola Longo, Gerardo Botti, Sandro Pignata, Sisto Perdonà, Stefania Scala
BACKGROUND: Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function. METHODS: VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-γ production...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yotam E Bar-Ephraim, Jasper J Koning, Estefany Burniol Ruiz, Tanja Konijn, Vera P Mourits, Kim A Lakeman, Louis Boon, Marijn Bögels, J Peter van Maanen, Joke M M Den Haan, Marjolein van Egmond, Gerd Bouma, Rogier M Reijmers, Reina E Mebius
Innate lymphoid cells (ILCs) guard epithelial tissue integrity during homeostasis, but can be potent immune effector cells during inflammation. Precursors to all ILC subsets (ILC precursors [ILCP]) have been identified in human peripheral blood (PB). We found that during homeostasis, ILCP in PB of mouse and human expressed homing receptors for secondary lymphoid organs, mainly CD62L. These ILCP entered mouse lymph nodes in a CD62L-dependent way and relied on S1P receptors for their exit. Importantly, CD62L expression was absent on human ILCs expressing NKp44 in tonsils and PB of Crohn disease patients, and relatively fewer CD62L+ ILCP were present in PB of Crohn disease patients...
November 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Marianne Forkel, Sophie van Tol, Charlotte Höög, Jakob Michaëlsson, Sven Almer, Jenny Mjösberg
Background and Aims: Innate lymphoid cells [ILC] have been suggested to play a role in inflammatory bowel disease [IBD]. Here, we investigated the ILC compartment in intestinal biopsies and blood from distinct patient groups with Crohn's disease [CD] and ulcerative colitis [UC], either newly diagnosed or with disease established for at least 1 year. This approach allowed us to simultaneously investigate temporal, disease-specific, and tissue-specific changes in ILC composition in IBD...
January 1, 2019: Journal of Crohn's & Colitis
Xiaohong Lv, Yun Gao, Tantan Dong, Libo Yang
BACKGROUND This study investigated the distribution and features of natural killer T (NKT) cells in the peripheral blood of diabetic patients, and their regulatory roles on vascular endothelial cells. MATERIAL AND METHODS Peripheral lymphocytes were isolated from diabetic patients. NKT cell distribution, proportion, and surface and intracellular markers were detected with flow cytometry. Peripheral blood-derived NKT cells were isolated and co-cultured with human umbilical vein endothelial cells (HUVECs). Proliferation and migration of HUVECs were assessed with the CCK-8 assay and the Transwell chamber assay...
November 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
David Cruz-Zárate, Graciela Libier Cabrera-Rivera, Bibiana Patricia Ruiz-Sánchez, Jeanet Serafín-López, Rommel Chacón-Salinas, Constantino López-Macías, Armando Isibasi, Humberto Gallegos-Pérez, Marco Antonio León-Gutiérrez, Eduardo Ferat-Osorio, Lourdes Arriaga-Pizano, Iris Estrada-García, Isabel Wong-Baeza
Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-α by monocytes and macrophages in response to TLR ligands...
October 29, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Elizabeth C Rosser, Hannah Lom, David Bending, Chantal L Duurland, Mona Bajaj-Elliott, Lucy R Wedderburn
OBJECTIVE: Evidence suggests that aberrant function of innate lymphoid cells (ILC), whose functional and transcriptional profile overlap with T helper (Th) cell subsets, contribute to immune-mediated pathologies. To date, analysis of Juvenile Idiopathic Arthritis (JIA) immune-pathology has concentrated on the contribution of CD4+ T-cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. Here, we extend this analysis to investigate a role for ILC and other IL-17 producing T-cell subsets...
October 22, 2018: Arthritis & Rheumatology
Iris C J Blijdorp, Silvia Menegatti, Leonike J J Van Mens, Marleen G H van de Sand, Sijia Chen, Hulda S Hreggvidsdottir, Troy Noordenbos, Talia E Latuhihin, Jochem H Bernink, Hergen Spits, Lars Rogge, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: Clinical trials of the anti-IL-17A antibody secukinumab demonstrated a crucial role of the IL-17A cytokine in the pathogenesis of spondyloarthritis (SpA), however its cellular source in this condition remains controversial. Group 3 innate lymphoid cells (ILC3s) have been recently identified in a number of different tissues as potent producers of proinflamatory cytokines, including IL-17A and IL-22. In this study we set out to characterize the presence and composition of ILCs and investigate whether these cells are an important source of IL-17A in the synovial tissue of patients with SpA...
September 27, 2018: Arthritis & Rheumatology
Gemma A Foulds, Jayakumar Vadakekolathu, Tarek M A Abdel-Fatah, Divya Nagarajan, Stephen Reeder, Catherine Johnson, Simon Hood, Paul M Moseley, Stephen Y T Chan, A Graham Pockley, Sergio Rutella, Stephanie E B McArdle
Background: Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically. Methods: Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls...
2018: Frontiers in Immunology
Silvia Gaggero, Maurizio Bruschi, Andrea Petretto, Monica Parodi, Genny Del Zotto, Chiara Lavarello, Carola Prato, Laura Santucci, Alessandra Barbuto, Cristina Bottino, Giovanni Candiano, Alessandro Moretta, Massimo Vitale, Lorenzo Moretta, Claudia Cantoni
The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement...
2018: Oncoimmunology
Samantha McQuaid, Sinead Loughran, Patrick Power, Paula Maguire, Dermot Walls, Maria Grazia Cusi, Claes Orvell, Patricia Johnson
No abstract text is available yet for this article.
September 2018: Journal of General Virology
Kenichiro Ito, Ryo Shiraishi, Koji Higai
Natural killer (NK) cells play an important role in tumor immunity and infection control. The natural cytotoxicity receptors (NCRs) NKp46, NKp44 and NKp30 are involved in the control of the activation of NK cells. Few reports have investigated the ligands of NCRs. We previously reported the NCRs binding affinity to heparin and glycosaminoglycans. We also showed that multimeric sialyl Lewis X-expressing transferrin, secreted by human hepatoma HepG2 cells, binds to NKp46 and NKp44, but not to NKp30. In this study, we investigated the binding between NCRs and glycolipids...
2018: Biological & Pharmaceutical Bulletin
Arum Park, Yunhee Lee, Mi Sun Kim, Young Ju Kang, Young-Jun Park, Haiyoung Jung, Tae-Don Kim, Hee Gu Lee, Inpyo Choi, Suk Ran Yoon
Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand...
2018: Frontiers in Immunology
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
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...
September 2018: Journal of Autoimmunity
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
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
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
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