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https://www.readbyqxmd.com/read/29142605/aviscumine-a-recombinant-ribosomal-inhibitor-increases-the-antitumor-activity-of-natural-killer-cells
#1
Gabriele Gamerith, Arno Amann, Bettina Schenk, Thomas Auer, Hans Lentzen, Dirk O Mügge, Katharina M Cima, Judith Löffler-Ragg, Wolfgang Hilbe, Heinz Zwierzina
Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142275/nf-%C3%AE%C2%BAb-protects-nkt-cells-from-tumor-necrosis-factor-receptor-1-induced-death
#2
Amrendra Kumar, Laura E Gordy, Jelena S Bezbradica, Aleksandar K Stanic, Timothy M Hill, Mark R Boothby, Luc Van Kaer, Sebastian Joyce
Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-xL-coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141219/preventive-inhibition-of-liver-tumorigenesis-by-systemic-activation-of-innate-immune-functions
#3
Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M Varki, Shuang-Jian Qiu, Bing Ren, Wenxian Fu, Gen-Sheng Feng
Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#4
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34(+) hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#5
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#6
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136142/the-forkhead-transcription-factor-foxo3-negatively-regulates-natural-killer-cell-function-and-viral-clearance-in-myocarditis
#7
Madlen Loebel, Luise Holzhauser, Jelka A Hartwig, Praphulla C Shukla, Konstantinos Savvatis, Alexander Jenke, Martina Gast, Felicitas Escher, Sonya C Becker, Sandra Bauer, Andrea Stroux, Antje Beling, Meike Kespohl, Sandra Pinkert, Henry Fechner, Uwe Kuehl, Dirk Lassner, Wolfgang Poller, Heinz-Peter Schultheiss, Tanja Zeller, Stefan Blankenberg, Anna-Pia Papageorgiou, Stephane Heymans, Ulf Landmesser, Carmen Scheibenbogen, Carsten Skurk
Aims: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. Methods and results: Effects of Foxo3 on viral load and immune responses were investigated in a model of coxsackie virus B3 myocarditis in wild-type (WT) and Foxo3 deficient mice. Reduced immune cell infiltration, viral titres, and pro-inflammatory cytokines in cardiac tissue were observed in Foxo3-/- mice 7 days post-infection (p...
November 9, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29134614/acute-exercise-during-hemodialysis-prevents-the-decrease-in-natural-killer-cells-in-patients-with-chronic-kidney-disease-a-pilot-study
#8
Maria Isabel Fuhro, Gilson P Dorneles, Francini P Andrade, Pedro R T Romão, Alessandra Peres, Mariane B Monteiro
PURPOSE: To evaluate the acute response of natural killer (NK) cell subsets of chronic kidney disease patients submitted to intradialytic exercise in a randomized crossover study. METHODS: Nine patients were submitted to a single bout of 20-min intradialytic exercise and a control hemodialysis (HD) session with an interval of 7 days between them. Peripheral blood sample was collected at baseline, during HD and immediately after HD in each trial to evaluate the peripheral frequency of NK cells and their subsets (CD3-CD56(bright) and CD3-CD56(dim)), systemic cortisol concentrations, C-reactive protein (CRP), creatine kinase activity (CK), and urea and creatinine levels...
November 13, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29133316/study-protocol-for-think-a-multinational-open-label-phase-i-study-to-assess-the-safety-and-clinical-activity-of-multiple-administrations-of-nkr-2-in-patients-with-different-metastatic-tumour-types
#9
Caroline Lonez, Bikash Verma, Alain Hendlisz, Philippe Aftimos, Ahmad Awada, Eric Van Den Neste, Gaetan Catala, Jean-Pascal H Machiels, Fanny Piette, Jason B Brayer, David A Sallman, Tessa Kerre, Kunle Odunsi, Marco L Davila, David E Gilham, Frédéric F Lehmann
INTRODUCTION: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29133294/proinflammatory-t-cell-status-associated-with-early-life-adversity
#10
Martha M C Elwenspoek, Xenia Hengesch, Fleur A D Leenen, Anna Schritz, Krystel Sias, Violetta K Schaan, Sophie B Mériaux, Stephanie Schmitz, Fanny Bonnemberger, Hartmut Schächinger, Claus Vögele, Jonathan D Turner, Claude P Muller
Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73)...
November 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29133133/boosting-natural-killer-cell-based-immunotherapy-with-anticancer-drugs-a-perspective
#11
REVIEW
Loredana Cifaldi, Franco Locatelli, Emiliano Marasco, Lorenzo Moretta, Vito Pistoia
Natural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29133053/synthesis-and-biological-evaluation-of-new-berberine-derivatives-as-cancer-immunotherapy-agents-through-targeting-ido1
#12
Yan-Xiang Wang, Wei-Qiang Pang, Qing-Xuan Zeng, Zhe-Song Deng, Tian-Yun Fan, Jian-Dong Jiang, Hong-Bin Deng, Dan-Qing Song
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#13
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29128662/activation-of-innate-immunity-in-primary-human-cells-using-a-plant-virus-derived-nanoparticle-tlr7-8-agonist
#14
Damien Carignan, Sabine Herblot, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Michel Duval, Pierre Savard, Denis Leclerc
Rod-shaped virus-like nanoparticles (VLNP) made of papaya mosaic virus (PapMV) coat proteins (CP) self-assembled around a single stranded RNA (ssRNA) were showed to be a TLR7 agonist. Their utilization as an immune modulator in cancer immunotherapy was showed promising. To establish a clinical relevance in human for PapMV VLNP, we showed that stimulation of human peripheral blood mononuclear cells (PBMC) with VLNP induces the secretion of interferon alpha (IFNα) and other pro-inflammatory cytokines and chemokines...
November 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29128554/immunomodulatory-effects-of-tyrosine-kinase-inhibitors-tkis-in-vitro-and-in-vivo-study
#15
Elena Marinelli Busilacchi, Andrea Costantini, Nadia Viola, Benedetta Costantini, Jacopo Olivieri, Luca Butini, Giorgia Mancini, Ilaria Scortechini, Martina Chiarucci, Monica Poiani, Antonella Poloni, Pietro Leoni, Attilio Olivieri
Pathogenesis of chronic Graft Versus Host Disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes, as well as B cells. Standard treatment is lacking for steroid dependent/refractory cases; potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent anti-fibrotic effect. However, TKI seems to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29127109/incb040093-is-a-novel-pi3k%C3%AE-inhibitor-for-the-treatment-of-b-cell-lymphoid-malignancies
#16
Niu Shin, Yun-Long Li, Song Mei, Kathy He Wang, Leslie Hall, Kamna Katiyar, Qian Wang, Gengjie Yang, Beth Rumberger, Lynn Leffet, Xin He, Mark Rupar, Kevin Bowman, Margaret Favata, Jun Li, Mike Liu, Yanlong Li, Maryanne Covington, Holly Koblish, Maxim Soloviev, Dana Shuey, Timothy Burn, Sharon Diamond, Jordan Fridman, Andrew Combs, Wenqing Yao, Swamy Yeleswaram, Gregory Hollis, Kris Vaddi, Reid Huber, Robert Newton, Peggy Scherle
PI3Kδ is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. Here, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74 to >900-fold selectivity against other PI3K family members...
November 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29124929/injectable-polymeric-cytokine-binding-nanowires-are-effective-tissue-specific-immunomodulators
#17
Colin R Zamecnik, Margaret M Lowe, David M Patterson, Michael D Rosenblum, Tejal A Desai
Injectable nanomaterials that interact with the host immune system without surgical intervention present spatially anchored complements to cell transplantation and could offer improved pharmacokinetics compared to systemic cytokine therapy. Here we demonstrate fabrication of high aspect ratio polycaprolactone nanowires coupled with cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. These structures are fabricated using a nanotemplating technique that allows for tunability of particle dimensions and utilize a straightforward maleimide conjugation chemistry to allow site-specific coupling to proteins...
November 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/29123966/pd-1-blockade-at-the-time-of-tumor-escape-potentiates-the-immune-mediated-antitumor-effects-of-a-melanoma-targeting-monoclonal-antibody
#18
Laetitia They, Henri-Alexandre Michaud, Ondine Becquart, Virginie Lafont, Bernard Guillot, Florence Boissière-Michot, Marta Jarlier, Caroline Mollevi, Jean-François Eliaou, Nathalie Bonnefoy, Laurent Gros
Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123946/tumor-cell-death-by-pattern-sensing-of-exogenous-rna-tumor-cell-tlr3-directly-induces-necroptosis-by-poly-i-c-in-vivo-independent-of-immune-effector-mediated-tumor-shrinkage
#19
Hiromi Takaki, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Poly(I:C) acts on dendritic cells to induce potent antitumor effects through the production of cytokines/interferons, activation of natural killer cells and proliferation of cytotoxic T lymphocytes. In some tumor or myeloid lineages, poly(I:C) seemed to induce necroptosis in concert with a pan-caspase inhibitor by directly acting on toll-like receptor (TLR) 3 in both in vivo and in vitro models.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123530/human-cardiac-derived-stem-progenitor-cells-fine-tune-monocyte-derived-descendants-activities-toward-cardiac-repair
#20
Noémie Dam, Hocine Rachid Hocine, Itziar Palacios, Olga DelaRosa, Ramón Menta, Dominique Charron, Armand Bensussan, Hicham El Costa, Nabila Jabrane-Ferrat, Wilfried Dalemans, Eleuterio Lombardo, Reem Al-Daccak
Cardiac repair following MI relies on a finely regulated immune response involving sequential recruitment of monocytes to the injured tissue. Monocyte-derived cells are also critical for tissue homeostasis and healing process. Our previous findings demonstrated the interaction of T and natural killer cells with allogeneic human cardiac-derived stem/progenitor cells (hCPC) and suggested their beneficial effect in the context of cardiac repair. Therefore, we investigated here whether monocytes and their descendants could be also modulated by allogeneic hCPC toward a repair/anti-inflammatory phenotype...
2017: Frontiers in Immunology
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