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https://www.readbyqxmd.com/read/28944953/nk-cells-produce-high-levels-of-il-10-early-after-allogeneic-stem-cell-transplantation-and-suppress-development-of-acute-gvhd
#1
Yl Tracey Chan, Jianmin Zuo, Charlotte Inman, Wayne Croft, Jusnara Begum, Joanne Croudace, Francesca Kinsella, Luke Maggs, Sandeep Nagra, Jane Nunnick, Ben Abbotts, Charles Craddock, Ram Malladi, Paul Moss
Natural killer (NK) cells rapidly reconstitute following allogeneic stem cell transplantation (allo-SCT), at the time when alloreactive T cell immunity is being established. We investigated very early NK cell reconstitution in 82 patients following T cell-depleted allo-SCT. NK cell number rapidly increased, exceeding T cell reconstitution such that the NK:T cell ratio was over 40 by day 14. NK cells at day 14 (NK-14) were donor-derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue...
September 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28943878/triplebody-mediates-increased-anti-leukemic-reactivity-of-il-2-activated-donor-natural-killer-nk-cells-and-impairs-viability-of-their-cd33-expressing-nk-subset
#2
Stephan Kloess, Alessa Ede Valverde da Silva, Olaf Oberschmidt, Tanja Gardlowski, Nadine Matthies, Maulik Vyas, Lubomir Arseniev, Michael Heuser, Elke Pogge von Strandmann, Ulrike Köhl
Natural killer cells (NK) are essential for the elimination of resistant acute myeloid and acute lymphoblastic leukemia (AML and ALL) cells. NK cell-based immunotherapies have already successfully entered for clinical trials, but limitations due to immune escape mechanisms were identified. Therefore, we extended our established NK cell protocol by integration of the previously investigated powerful trispecific immunoligand ULBP2-aCD19-aCD33 [the so-called triplebodies (TBs)] to improve the anti-leukemic specificity of activated NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28943093/naturak-killer-cell-immunotherapies-against-cancer-checkpoint-inhibitors-and-more
#3
REVIEW
Laura Chiossone, Margaux Vienne, Yann M Kerdiles, Eric Vivier
After many years of research, recent advances have shed new light on the role of the immune system in advanced-stage cancer. Various types of immune cells may be useful for therapeutic purposes, along with chemical molecules and engineered monoclonal antibodies. The immune effectors suitable for manipulation for adoptive transfer or drug targeting in vivo include natural killer (NK) cells. These cells are of particular interest because they are tightly regulated by an array of inhibitory and activating receptors, enabling them to kill tumor cells while sparing normal cells...
September 21, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#4
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28941928/sequential-actions-of-immune-effector-cells-induced-by-viral-activation-of-dendritic-cells-to-eliminate-murine-neuroblastoma
#5
Naonori Kawakubo, Sakura Tanaka, Yoshiaki Kinoshita, Tatsuro Tajiri, Yoshikazu Yonemitsu, Tomoaki Taguchi
PURPOSE: In preclinical trails, we reported the antitumor effect of dendritic cells activated with Sendai virus (rSeV/DC) combined with γ-irradiation against neuroblastoma. However, what kind of effector cells for the combined therapy were used to show the antitumor effect was unclear. In this study, we performed radiation and rSeV/DC therapy in vivo and examined the effector cells involved. METHODS: Dendritic cells were cultured from bone marrow cells, activated with SeV and administered intratumorally at 10(6) weekly for 3weeks...
August 26, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28940695/herpes-zoster-in-kidney-transplant-recipients-protective-effect-of-anti-cmv-prophylaxis-and-nk-cells-count-a-single-center-cohort-study
#6
Mario Fernández-Ruiz, Julia Origüen, David Lora, Francisco López-Medrano, Esther González, Natalia Polanco, Rafael San Juan, Tamara Ruiz-Merlo, Patricia Parra, Amado Andrés, José María Aguado
Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post-transplant year) and late HZ (years 1 to 5) were separately assessed. We observed 35 episodes of post-transplant HZ after a median follow-up of 48...
September 22, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28940004/adjuvant-therapy-in-biliary-atresia-hopelessly-optimistic-or-potential-for-change
#7
REVIEW
Mark Davenport
Given that the aetiology of biliary atresia (BA) is complex and that there is a multiplicity of possible pathogenic mechanisms then it is perhaps not surprising that the evidence for effect of a number of different agents is contradictory. Post-operative cholangitis for instance is common, bacterial in origin and various antibiotic regimens have been tested (although none in a randomized trial) but continuation beyond the early post-operative period does not appear to offer any greater protection. There is an inflammatory reaction in about 25-35% of cases of BA illustrated by abnormal expression of class II antigen and upregulation of ICAM, VCAM and E-selectin with an infiltrate of immune-activated T cells (predominantly CD4 + Th1 and Th17) and NK cells and a systemic surge in inflammatory cytokines (e...
September 22, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28939747/a-pilot-trial-of-humanized-anti-gd2-monoclonal-antibody-hu14-18k322a-with-chemotherapy-and-natural-killer-cells-in-children-with-recurrent-refractory-neuroblastoma
#8
Sara M Federico, M Beth McCarville, Barry L Shulkin, Paul M Sondel, Jacquelyn A Hank, Paul Hutson, Michael Meagher, Aaron Shafer, Catherine Y Ng, Wing Leung, William E Janssen, Jianrong Wu, Shenghua Mao, Rachel C Brennan, Victor M Santana, Alberto Pappo, Wayne L Furman
PURPOSE: Anti-GD2 monoclonal antibodies (mAb), acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines and haploidentical natural killer (NK) cells. EXPERIMENTAL DESIGN: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40mg/m2/dose, days 2-5), GMCSF and IL-2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4) and ifosfamide/carboplatin/etoposide (courses 5,6)...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939254/inhibition-of-mek-erk1-2-map-kinase-signalling-pathway-reduces-rabies-virus-induced-pathologies-in-mouse-model
#9
Venkataravanappa Manjunatha, Karam Pal Singh, Mani Saminathan, Rajendra Singh, Nayakwadi Shivasharanappa, Channakeshava Sokke Umeshappa, Kuldeep Dhama, Gundallahalli Bayyappa Manjunathareddy
The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (RV) infection in vivo is not clear. In the present study, we investigated the potential role of MEK-ERK1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. Mice were infected with 25 LD50 of challenge virus standard (CVS) strain of RV by intracerebral (i...
September 19, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28938026/hiv-exposed-seronegative-hesn-compared-to-hiv-infected-individuals-have-higher-frequencies-of-telomeric-killer-immunoglobulin-like-receptor-kir-b-motifs-contribution-of-kir-b-motif-encoded-genes-to-nk-cell-responsiveness
#10
Elise Jackson, Cindy Xinyu Zhang, Zahra Kiani, Irene Lisovsky, Benjamin Tallon, Alexa Del Corpo, Louise Gilbert, Julie Bruneau, Réjean Thomas, Pierre Côté, Benoit Trottier, Roger LeBlanc, Danielle Rouleau, Cécile Tremblay, Christos M Tsoukas, Jean-Pierre Routy, Xiaoyan Ni, Tsoarello Mabanga, Nicole F Bernard
Previously, we showed that Killer Immunoglobulin-like Receptor (KIR)3DS1 homozygotes (hmz) are more frequent in HIV exposed seronegative (HESN) than in recently HIV infected (HIV+) individuals. KIR3DS1 encodes an activating Natural Killer (NK) cell receptor (NKR). The link between KIR genotype and HIV outcomes likely arises from the function that NK cells acquire through expression of particular NKRs. An initial screen of 97 HESN and 123 HIV+ subjects for the frequency of KIR region gene carriage observed between-group differences for several telomeric KIR region loci...
2017: PloS One
https://www.readbyqxmd.com/read/28936583/effective-immunological-guidance-of-genetic-analyses-including-exome-sequencing-in-patients-evaluated-for-hemophagocytic-lymphohistiocytosis
#11
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Christian Klemann, Sebastian F N Bode, Carsten Speckmann, Gritta Janka, Katharina Wustrau, Mirzokhid Rakhmanov, Ilka Fuchs, Hans C Hennies, Stephan Ehl
We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results...
September 21, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28935883/ex-vivo-expanded-human-nk-cells-survive-and-proliferate-in-humanized-mice-with-autologous-human-immune-cells
#12
Fatemeh Vahedi, Tina Nham, Sophie M Poznanski, Marianne V Chew, Mira M Shenouda, Dean Lee, Ali A Ashkar
Adoptive immune cell therapy is emerging as a promising immunotherapy for cancer. Particularly, the adoptive transfer of NK cells has garnered attention due to their natural cytotoxicity against tumor cells and safety upon adoptive transfer to patients. Although strategies exist to efficiently generate large quantities of expanded NK cells ex vivo, it remains unknown whether these expanded NK cells can persist and/or proliferate in vivo in the absence of exogenous human cytokines. Here, we have examined the adoptive transfer of ex vivo expanded human cord blood-derived NK cells into humanized mice reconstituted with autologous human cord blood immune cells...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#13
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28935344/tailoring-natural-killer-cell-immunotherapy-to-the-tumour-microenvironment
#14
REVIEW
Alexander David Barrow, Marco Colonna
Natural killer (NK) cells are cytotoxic and cytokine-secreting cells that can mediate potent anti-tumour activity. Accumulating evidence indicates that NK cell functions are severely compromised within the confines of the tumour microenvironment thus impairing the efficacy and development of NK cell-based therapies. Here we review the various cellular and molecular pathways that tumours have supplanted to evade NK cell surveillance. We highlight novel strategies designed to alleviate or circumvent the immunosuppressive conditions of the tumour microenvironment in order to emancipate NK cell function and stifle the inexorable growth and metastasis of malignant cells...
September 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28935248/comparison-of-t-lymphocyte-subsets-in-aplastic-anemia-and-hypoplastic-myelodysplastic-syndromes
#15
Hai-Fang Zhang, Zhen-Dong Huang, Xue-Run Wu, Qian Li, Zhi-Feng Yu
AIMS: This study aims to compare the proportion of peripheral blood T lymphocyte subsets and related blood cell and bone marrow cytology indexes between patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS), and investigate the clinical identification significance. MATERIALS AND METHODS: A total of 41 patients with AA and 46 patients with hypo-MDS were collected, and the proportions of peripheral blood T lymphocyte subsets, CD3(-)CD16/CD56(+)NK cells, CD3(+)CD57(+)T-LGL cells and CD19(+)B lymphocytes were detected by flow cytometry...
September 18, 2017: Life Sciences
https://www.readbyqxmd.com/read/28934678/establishment-of-cell-line-with-nk-nkt-phenotype-from-myeloid-nk-cell-acute-leukemia
#16
A Darji, N Desai, R Modi, B Khamar, S Rajkumar
Acute Myeloid Leukemia (AML) is the most common malignancy in adults with a 5-year survival rate of 27% of the total affected population. For effective treatment and new drug discovery, cell lines are considered as a very important tool. Here we report an establishment of a continuous human cell line AML-004 with a hypo-diploid chromosome 44 and presence of both NK/NKT phenotypes. The cell line was isolated from the blood sample of myeloid NK cell acute leukemia patients and extensively characterized by flow cytometery, morphology, and cytogentic analysis...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#17
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28934507/a-comprehensive-cell-specific-microrna-catalogue-of-human-peripheral-blood
#18
Simonas Juzenas, Geetha Venkatesh, Matthias Hübenthal, Marc P Hoeppner, Zhipei Gracie Du, Maren Paulsen, Philip Rosenstiel, Philipp Senger, Martin Hofmann-Apitius, Andreas Keller, Limas Kupcinskas, Andre Franke, Georg Hemmrich-Stanisak
With this study, we provide a comprehensive reference dataset of detailed miRNA expression profiles from seven types of human peripheral blood cells (NK cells, B lymphocytes, cytotoxic T lymphocytes, T helper cells, monocytes, neutrophils and erythrocytes), serum, exosomes and whole blood. The peripheral blood cells from buffy coats were typed and sorted using FACS/MACS. The overall dataset was generated from 450 small RNA libraries using high-throughput sequencing. By employing a comprehensive bioinformatics and statistical analysis, we show that 3' trimming modifications as well as composition of 3' added non-templated nucleotides are distributed in a lineage-specific manner-the closer the hematopoietic progenitors are, the higher their similarities in sequence variation of the 3' end...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933961/17%C3%AE-estradiol-induces-proliferation-of-endometrial-nk-cells-cd56-in-postmenopausal-women
#19
T Sho, T Hachisuga, C Koi, T Kurita, S Kagami, T Kawagoe, Y Matsuura, K Yoshimura, M Hisaoka
OBJECTIVE: The aim of this report was to evaluate the impact of hormone replacement therapy (HRT) on lymphocytic infiltration of the endometrium in postmenopausal women. METHOD: This study included 58 Japanese patients who had undergone hysterectomy at the University Hospital of Occupational and Environmental Health, Japan. Before surgery, nine patients had received 17β-estradiol (E2), 0.72 mg transdermally for 2-8 weeks (E2 group); 16 patients had received an Estra-1,3,5(10)-triene-3,16α, 17β-triol (E3) vaginal tablet 0...
September 21, 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#20
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
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