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https://www.readbyqxmd.com/read/29926278/transforming-growth-factor-%C3%AE-and-tumor-necrosis-factor-%C3%AE-reduce-the-sensitivity-of-miapaca2-pancreatic-cancer-cells-to-lysis-by-nk-cells
#1
E O Ostapchuk, A Kali, N N Belyaev
We studied the role of cytokines TGF-β and TNFα in reduction of the cytolytic activity of NK cells towards tumor cells. Exogenous TGF-β and TNFα reduced the sensitivity of MiaPaCa2 pancreatic adenocarcinoma cells to NK cytotoxicity, which was associated with reduction of ULBP-1 expression and increase of HLA-E, HLA-G, CD155, and CD112 expression on Mia-PaCa2 cells. Changes in the expression of ligands for NK receptors on tumor cells induced by TGF-β and TNFα may contribute to reduction of cytotoxicity of tumor-associated NK cells and thus prevent an adequate antitumor immune response leading to the disease progress...
June 20, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29863952/role-of-osteocyte-pdl-crosstalk-in-tooth-movement-via-sost-sclerostin
#2
N Odagaki, Y Ishihara, Z Wang, E Ei Hsu Hlaing, M Nakamura, M Hoshijima, S Hayano, N Kawanabe, H Kamioka
Sclerostin (Scl) negatively regulates bone formation and favors bone resorption. Osteocytes, the cells responsible for mechanosensing, are known as the primary source of Scl and are a key regulator of bone remodeling through the induction of receptor activator of NF-κB ligand (RANKL). However, the spatiotemporal patterns of Scl in response to mechanical stimuli and their regulatory mechanisms remain unknown. We investigated the regulatory dynamics of the SOST/Scl expression generated by orthodontic tooth movement (OTM) in vivo and in vitro...
June 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29805553/recent-advances-in-cd8-regulatory-t-cell-research
#3
REVIEW
Yating Yu, Xinbo Ma, Rufei Gong, Jianmeng Zhu, Lihua Wei, Jinguang Yao
Various subgroups of CD8+ T lymphocytes do not only demonstrate cytotoxic effects, but also serve important regulatory roles in the body's immune response. In particular, CD8+ regulatory T cells (CD8+ Tregs), which possess important immunosuppressive functions, are able to effectively block the overreacting immune response and maintain the body's immune homeostasis. In recent years, studies have identified a small set of special CD8+ Tregs that can recognize major histocompatibility complex class Ib molecules, more specifically Qa-1 in mice and HLA-E in humans, and target the self-reactive CD4+ T ce lls...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29789149/the-expanding-role-of-murine-class-ib-mhc-in-the-development-and-activation-of-natural-killer-cells
#4
REVIEW
Katharine J Goodall, Angela Nguyen, Lucy C Sullivan, Daniel M Andrews
Major Histocompatibility Complex-I (MHC-I) molecules can be divided into class Ia and class Ib, with three distinct class Ib families found in the mouse. These families are designated as Q, T and M and are largely unexplored in terms of their immunological function. Among the class Ib MHC, H2-T23 (Qa-1b) has been a significant target for Natural Killer (NK) cell research, owing to its homology with the human class Ib human leukocyte antigen (HLA)-E. However, recent data has indicated that members of the Q and M family of class Ib MHC also play a critical role in the development and regulation NK cells...
May 19, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#5
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29760609/identification-of-potential-crucial-genes-and-construction-of-microrna-mrna-negative-regulatory-networks-in-osteosarcoma
#6
Yue Pan, Lingyun Lu, Junquan Chen, Yong Zhong, Zhehao Dai
Background: This study aimed to identify potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma by comprehensive bioinformatics analysis. Methods: Data of gene expression profiles (GSE28424) and miRNA expression profiles (GSE28423) were downloaded from GEO database. The differentially expressed genes (DEGs) and miRNAs (DEMIs) were obtained by R Bioconductor packages. Functional and enrichment analyses of selected genes were performed using DAVID database...
2018: Hereditas
https://www.readbyqxmd.com/read/29737525/cytomegalovirus-an-unlikely-ally-in-the-fight-against-blood-cancers
#7
Austin B Bigley, Forrest L Baker, Richard J Simpson
CMV infection is a potentially fatal complication in patients receiving HSCT, but recent evidence indicates that CMV has strong anti-leukemia effects due in part to shifts in the composition of NK-cell subsets. NK-cells are the primary mediators of the anti-leukemia effect of allogeneic HSCT and infusion of allogeneic NK-cells has shown promise as a means of inducing remission and preventing relapse of several different hematologic malignancies. The effectiveness of these treatments is limited, however, when tumors express HLA-E, a ligand for the inhibitory receptor NKG2A which is expressed by the vast majority of post-transplant reconstituted and ex vivo expanded NK-cells...
May 8, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29709038/hcmv-triggers-frequent-and-persistent-ul40-specific-unconventional-hla-e-restricted-cd8-t-cell-responses-with-potential-autologous-and-allogeneic-peptide-recognition
#8
Nicolas Jouand, Céline Bressollette-Bodin, Nathalie Gérard, Magali Giral, Pierrick Guérif, Audrey Rodallec, Romain Oger, Tiphaine Parrot, Mathilde Allard, Anne Cesbron-Gautier, Nadine Gervois, Béatrice Charreau
Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-EUL40) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-EUL40 CD8 T-cell responses remain mostly unknown...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29610856/natural-killer-cell-inhibition-by-hla-e-molecules-on-induced-pluripotent-stem-cell-derived-retinal-pigment-epithelial-cells
#9
Sunao Sugita, Kenichi Makabe, Yuko Iwasaki, Shota Fujii, Masayo Takahashi
Purpose: To determine whether human induced pluripotent stem (iPS) cell-derived retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) cell activation. Methods: iPS-RPE cells were cocultured with peripheral blood mononuclear cells (PBMCs) or purified NK cells from healthy donors after stimulation with cytokines. To confirm expression of NK cell-specific markers, flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 expression with flow cytometry, and NK suppression by RPE cells was assessed for granzyme B production with ELISA...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29587858/hla-and-proteasome-expression-body-map
#10
Sebastian Boegel, Martin Löwer, Thomas Bukur, Patrick Sorn, John C Castle, Ugur Sahin
BACKGROUND: The presentation of HLA peptide complexes to T cells is a highly regulated and tissue specific process involving multiple transcriptionally controlled cellular components. The extensive polymorphism of HLA genes and the complex composition of the proteasome make it difficult to map their expression profiles across tissues. METHODS: Here we applied a tailored gene quantification pipeline to 4323 publicly available RNA-Seq datasets representing 55 normal tissues and cell types to examine expression profiles of (classical and non-classical) HLA class I, class II and proteasomal genes...
March 27, 2018: BMC Medical Genomics
https://www.readbyqxmd.com/read/29562195/unconventional-t-cell-targets-for-cancer-immunotherapy
#11
REVIEW
Dale I Godfrey, Jérôme Le Nours, Daniel M Andrews, Adam P Uldrich, Jamie Rossjohn
Most studies on the immunotherapeutic potential of T cells have focused on CD8 and CD4 T cells that recognize peptide antigens (Ag) presented by polymorphic major histocompatibility complex (MHC) class I and MHC class II molecules, respectively. However, unconventional T cells, which interact with MHC class Ib and MHC-I like molecules, are also implicated in tumor immunity, although their role therein is unclear. These include unconventional T cells targeting MHC class Ib molecules such as HLA-E and its murine ortholog Qa-1b, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, and γδ T cells...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29545802/potential-beneficial-effects-of-cytomegalovirus-infection-after-transplantation
#12
REVIEW
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536572/multiple-genetically-modified-gtko-hcd46-hla-e-h%C3%AE-2-mg-porcine-hearts-are-protected-from-complement-activation-and-natural-killer-cell-infiltration-during-ex-vivo-perfusion-with-human-blood
#13
Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29514694/aberrant-stat-phosphorylation-signaling-in-peripheral-blood-mononuclear-cells-from-multiple-sclerosis-patients
#14
Ester Canto, Noriko Isobe, Alessandro Didonna, Stephen L Hauser, Jorge R Oksenberg
BACKGROUND: Multiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins. METHODS: We developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients...
March 7, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29499226/clinicopathologic-significance-of-hla-g-and-hla-e-molecules-in-tunisian-patients-with-ovarian-carcinoma
#15
Wafa Babay, Hamza Ben Yahia, Nadia Boujelbene, Nour Zidi, Ahmed Baligh Laaribi, Dhikra Kacem, Radhia Ben Ghorbel, Abdellatif Boudabous, Hadda-Imene Ouzari, Roberta Rizzo, Vera Rebmann, Karima Mrad, Inès Zidi
BACKGROUND: The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. METHODS: HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues...
June 2018: Human Immunology
https://www.readbyqxmd.com/read/29491867/acquired-natural-killer-cell-dysfunction-in-the-tumor-microenvironment-of-classic-hodgkin-lymphoma
#16
REVIEW
Jodi Chiu, Daniel M Ernst, Armand Keating
An understanding of interactions within the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL) has helped pave the way to novel immunotherapies that have enabled dormant and tumor-tolerant immune cells to be reactivated. The immunosuppressive nature of the TME in cHL specifically inhibits the proliferation and activity of natural killer (NK) cells, which contributes to tumor immune-escape mechanisms. This deficiency of NK cells begins at the tumor site and progresses systemically in patients with advanced disease or adverse prognostic factors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459477/intrinsic-functional-potential-of-nk-cell-subsets-constrains-retargeting-driven-by-chimeric-antigen-receptors
#17
Vincent Yi Sheng Oei, Marta Siernicka, Agnieszka Graczyk-Jarzynka, Hanna Julie Hoel, Weiwen Yang, Daniel Palacios, Hilde Almåsbak, Malgorzata Bajor, Dennis Clement, Ludwig Brandt, Björn Önfelt, Jodie Goodridge, Magdalena Winiarska, Radoslaw Zagozdzon, Johanna Olweus, Jon-Amund Kyte, Karl-Johan Malmberg
Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles...
April 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29453317/histone-h3-3k27m-mobilizes-multiple-cancer-testis-ct-antigens-in-pediatric-glioma
#18
Houliang Deng, Jianming Zeng, Ting Zhang, Longcai Gong, Hongjie Zhang, Edwin Cheung, Chris Jones, Gang Li
Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drives the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#19
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina Wikström, Pontus Blomberg, Björn Engelbrekt Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2-activated haploidentical NK cells. Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients...
April 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29422902/t-cells-engaging-the-conserved-mhc-class-ib-molecule-qa-1-b-with-tap-independent-peptides-are-semi-invariant-lymphocytes
#20
Elien M Doorduijn, Marjolein Sluijter, Bianca J Querido, Ursula J E Seidel, Claudia C Oliveira, Sjoerd H van der Burg, Thorbald van Hall
The HLA-E homolog in the mouse (Qa-1b ) is a conserved MHC class Ib molecule presenting monomorphic peptides to germline-encoded natural killer receptor CD94/NKG2A. Previously, we demonstrated the replacement of this canonical peptide by a diverse peptidome upon deficiency of the TAP peptide transporter. Analysis of this Qa-1b -restricted T cell repertoire against these non-mutated neoantigens revealed characteristics of conventional hypervariable CD8+ T cells, but also of invariant T cell receptor (TCR)αβ T cells...
2018: Frontiers in Immunology
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