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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/29456536/janus-faced-myeloid-derived-suppressor-cell-exosomes-for-the-good-and-the-bad-in-cancer-and-autoimmune-disease
#1
REVIEW
Margot Zöller
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29455234/blastic-plasmacytoid-dendritic-cell-neoplasm-update-on-therapy-especially-novel-agents
#2
REVIEW
Shunan Wang, Xingtong Wang, Mingsuo Liu, Ou Bai
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short...
February 17, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29452664/the-role-of-stem-cell-transplantation-in-follicular-lymphoma
#3
REVIEW
Georg Hess
With the introduction of novel treatments paradigms to if or when to use transplantation strategies for patients with follicular lymphoma have changed substantially. Autologous transplantation has been intensively evaluated as consolidation after first induction treatment with positive effects, however the introduction of Rituximab led to comparable improvements and HDT has been moved to relapse treatment. In this indication HDT was frequently use already at first relapse, but now is dominantly used in patients with a highrisk profile, e...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29446493/anti-donor-antibody-induction-following-intramuscular-injections-of-allogeneic-mesenchymal-stromal-cells
#4
Senthilkumar Alagesan, Clara Sanz-Nogués, Xizhe Chen, Michael Creane, Thomas Ritter, Rhodri Ceredig, Timothy O'Brien, Matthew D Griffin
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice two weeks after single or repeated IM injections of fully-MHC-mismatched allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline...
February 15, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#5
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 I Wikstrom, Pontus Blomberg, Bjorn E 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 IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439842/zinc-supplementation-plays-a-crucial-role-in-t-helper-9-differentiation-in-allogeneic-immune-reactions-and-non-activated-t-cells
#6
Martina Maywald, Fudi Wang, Lothar Rink
T helper (Th) 9 cells play a critical role in immune-mediated diseases, including allergic airway inflammation, autoimmune diseases, and cancer development. Thus, the promotion or suppression of Th9 cell differentiation, transcriptional control, and function is very important for a healthy immune system. Interestingly, T cell maturation, differentiation and function are highly dependent on the individuals' zinc status. This is especially seen in zinc deficient individuals as in the elderly population often suffering of autoimmunity and increased incidence of infections...
February 6, 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29437593/%C3%AE-1-antitrypsin-infusion-for-treatment-of-steroid-resistant-acute-graft-versus-host-disease
#7
John M Magenau, Steven C Goldstein, Dan Peltier, Robert J Soiffer, Thomas Braun, Attaphol Pawarode, Mary M Riwes, Maggi Kennel, Joseph H Antin, Corey S Cutler, Vincent T Ho, Edwin P Alyea, Brian L Parkin, Gregory A Yanik, Sung Won Choi, Eli C Lewis, Charles A Dinarello, John Koreth, Pavan Reddy
Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells...
February 2, 2018: Blood
https://www.readbyqxmd.com/read/29435996/type-ii-minimal-invasive-extracorporeal-circuit-for-aortic-valve-replacement-a-randomized-controlled-trial
#8
Erich Gygax, Hans-Ulrich Kaeser, Mario Stalder, Brigitta Gahl, Robert Rieben, Thierry Carrel, Gabor Erdoes
Extracorporeal circulation triggers systemic inflammatory response and coagulation disorders which may lead to unfavorable clinical outcome. A type II minimally-invasive extracorporeal circuit (MiECC) is a closed system with markedly reduced artificial surface as compared to conventional extracorporeal circuits (CECC). The aim of this study was to investigate and compare inflammatory responses, complement activation and selected clinical end-points in isolated surgical aortic valve replacement (SAVR) performed with a type II MiECC circuit or a CECC...
February 12, 2018: Artificial Organs
https://www.readbyqxmd.com/read/29433372/characterization-of-innate-immune-viral-sensors-in-patients-following-allogeneic-hematopoietic-stem-cell-transplantation
#9
Sarah L Caddy, Meng Wang, Pramila Krishnamurthy, Benjamin Uttenthal, Anita Chandra, Charles Crawley, Leo C James
Viral infection is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplant (HSCT), with up to one in four deaths directly linked to viral disease. Whilst awaiting lymphocyte reconstitution post-HSCT, the innate antiviral immune response is the first line of defense against invading viruses. Several novel innate viral-sensing pathways have recently been characterized, but their physiological importance in humans is poorly understood. We analyzed a panel of innate viral-sensor genes in HSCT patients, and assessed whether differences in innate antiviral responses could account for variation in susceptibility to viral infections...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29431743/sorafenib-promotes-graft-versus-leukemia-activity-in-mice-and-humans-through-il-15-production-in-flt3-itd-mutant-leukemia-cells
#10
Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis Dong Hwan Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Sha, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29423555/second-malignancies-after-hematopoietic-stem-cell-transplantation
#11
REVIEW
Ivetta Danylesko, Avichai Shimoni
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5-10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers...
February 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29420106/syncytial-variant-of-nodular-sclerosing-hodgkin-lymphoma-in-children-a-prognostic-factor
#12
Noa Granot, Ayelet Ben-Barak, Yael Fisher, Hana Golan, Myriam Weyl Ben-Arush
Nodular sclerosing Hodgkin lymphoma (HL) has an excellent prognosis in children. The syncytial variant (SV) of HL in adults represents a clinic pathologic entity with a worse outcome. We report the clinical features and the course of the disease of three children with refractory HL. The three patients with SV were analyzed in a retrospective multi-institutional study conducted in Israel in 51 children diagnosed with refractory or recurrent HL between 1997 and 2014. All the three children developed multiple recurrences soon after diagnosis...
February 8, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29417766/limiting-glioma-development-by-photodynamic-therapy-generated-macrophage-vaccine-and-allo-stimulation-an-in-vivo-histological-study-in-rats
#13
Steen J Madsen, Catherine Christie, Khoi Huynh, Qian Peng, Francisco A Uzal, Tatiana B Krasieva, Henry Hirschberg
Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site...
February 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29417689/efficacy-of-high-dose-steroids-for-bronchiolitis-obliterans-syndrome-post-pediatric-hematopoietic-stem-cell-transplantation
#14
Ehud Even-Or, Hasan Ghandourah, Muhammad Ali, Joerg Krueger, Neil B Sweezey, Tal Schechter
BOS is the pulmonary manifestation of cGvHD post-allogeneic HSCT. Survival and treatment of this often fatal complication have not improved over the last 20 years and there is no clear standard of care. For the past 10 years, BOS was treated in our center with monthly cycles of HDPS. We reviewed the outcomes of patients with post-HSCT BOS who met the diagnostic criteria for BOS as per the NIH consensus and were treated with at least one cycle of methylprednisolone at a dose of 10-30 mg/kg/d×3 d. We collected demographic and clinical data, responses to treatment and results of pulmonary function tests at several time points...
February 7, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29416605/human-dkk1-and-human-hsp70-fusion-dna-vaccine-induces-an-effective-anti-tumor-efficacy-in-murine-multiple-myeloma
#15
Ting-Ting Liu, Yang Wu, Ting Niu
Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415891/efficacy-of-intracellular-immune-checkpoint-silenced-dc-vaccine
#16
Danhong Wang, Xue F Huang, Bangxing Hong, Xiao-Tong Song, Liangding Hu, Min Jiang, Bin Zhang, Hongmei Ning, Yuhang Li, Chen Xu, Xiao Lou, Botao Li, Zhiyong Yu, Jiangwei Hu, Jianlin Chen, Fan Yang, Haiyan Gao, Guoliang Ding, Lianming Liao, Lisa Rollins, Lindsey Jones, Si-Yi Chen, Hu Chen
BACKGROUND: DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency. METHODS: We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy. The adenovirus (Ad-siSSF) delivers two tumor-associated antigens (TAAs), survivin and MUC1; secretory bacterial flagellin for DC maturation; and an RNA interference moiety to suppress SOCS1...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29412476/soluble-mhc-class-ii-driven-therapy-for-a-systemic-lupus-erythematosus-murine-experimental-in-vitro-and-in-vivo-model
#17
Katerina Bakela, Myrsini Dimakopoulou, Panagiota Batsou, Nikos Manidakis, Irene Athanassakis
Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, the present study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA respectively...
February 7, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29411417/chronic-myeloid-leukemia-2018-update-on-diagnosis-therapy-and-monitoring
#18
Elias Jabbour, Hagop Kantarjian
DISEASE OVERVIEW: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. DIAGNOSIS: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome...
March 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29410665/the-role-of-micrornas-in-myeloid-cells-during-graft-versus-host-disease
#19
REVIEW
Sophia Chen, Robert Zeiser
The successful treatment of various hematologic diseases with allogeneic hematopoietic cell transplantation is often limited by the occurrence of graft-versus-host disease (GvHD). Several microRNAs (miRs) have recently been shown to impact the biology of GvHD by regulating pro- as well as anti-inflammatory target genes. There is increasing evidence that a single miR can have different effects by preferentially targeting certain genes depending on the cell type that the miR is analyzed in. This review will focus on the role of miRs in myeloid cells during the development of acute and chronic GvHD and autoimmune diseases...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29407325/dexamethasone-prolongs-cardiac-allograft-survival-in-a-murine-model-through-myeloid-derived-suppressor-cells
#20
T Nakao, T Nakamura, K Masuda, T Matsuyama, H Ushigome, E Ashihara, N Yoshimura
BACKGROUND: Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood. MATERIAL AND METHODS: In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant...
January 2018: Transplantation Proceedings
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