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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/29237505/1-25-dihydroxyvitamin-d3-modulates-the-phenotype-and-function-of-monocyte-derived-dendritic-cells-in-cattle
#1
Yolanda Corripio-Miyar, Richard J Mellanby, Katy Morrison, Tom N McNeilly
BACKGROUND: The active form of the vitamin D3, 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to have major effects not only on physiological processes but also on the regulation of the immune system of vertebrates. Dendritic cells are specialised antigen presenting cells which are in charge of the initiation of T-cell dependant immune responses and as such are key regulators of responses towards pathogens. In this study we set out to evaluate the effects of 1,25-(OH)2D3 on the phenotype of cattle monocyte-derived dendritic cells (MoDCs) and how the conditioning with this vitamin affects the function of these myeloid cells...
December 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29233904/autologous-dendritic-cells-pulsed-with-allogeneic-tumor-cell-lysate-in-mesothelioma-from-mouse-to-human
#2
Joachim G Aerts, Pauline L de Goeje, Robin Cornelissen, Margaretha E H Kaijen-Lambers, Koen Bezemer, Cor van der Leest, Niken M Mahaweni, Andre Kunert, Ferry A L M Eskens, Cynthia Waasdorp, Eric Braakman, Bronno van der Holt, Arnold G Vulto, Rudi W Hendriks, Joost P J J Hegmans, Henk C Hoogsteden
PURPOSE: Mesothelioma has been regarded as a non-immunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis.  Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response towards malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29232178/rapid-decrease-in-krt14-and-tp53-mrna-expression-in-the-buccal-mucosa-of-patients-receiving-total-body-irradiation-for-allogeneic-stem-cell-transplantation
#3
J Chmara, J W L Browning, H Atkins, M Sabloff, B C McKay
The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis...
December 12, 2017: Radiation Research
https://www.readbyqxmd.com/read/29225601/anti-donor-immune-responses-elicited-by-allogeneic-mesenchymal-stem-cells-and-their-extracellular-vesicles-are-we-still-learning
#4
REVIEW
Paul Lohan, Oliver Treacy, Matthew D Griffin, Thomas Ritter, Aideen E Ryan
Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous) MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#5
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222293/current-treatment-algorithm-for-the-management-of-lower-risk-mds
#6
REVIEW
Aristoteles Giagounidis
Lower risk myelodysplastic syndromes (MDS), defined as MDS with a Revised International Prognostic Scoring System score ≤3.5 points, will remain a challenging entity in 2018. Supportive care continues to be the linchpin of treatment, although the options to reduce transfusion needs are broadening. To achieve red blood cell transfusion independence in non-del(5q) patients, erythropoiesis-stimulating agents remain a mainstay of therapy as long as endogenous erythropoietin levels are <500 U/L (and preferably <200 U/L)...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222233/current-management-of-philadelphia-chromosome-positive-all-and-the-role-of-stem-cell-transplantation
#7
REVIEW
Farhad Ravandi
Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221730/ablation-of-transcription-factor-irf4-promotes-transplant-acceptance-by-driving-allogenic-cd4-t-cell-dysfunction
#8
Jie Wu, Hedong Zhang, Xiaomin Shi, Xiang Xiao, Yihui Fan, Laurie J Minze, Jin Wang, Rafik M Ghobrial, Jiahong Xia, Roger Sciammas, Xian C Li, Wenhao Chen
CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction...
December 4, 2017: Immunity
https://www.readbyqxmd.com/read/29217388/impact-of-cytomegalovirus-cmv-viral-load-on-probability-of-spontaneous-clearance-and-response-to-pre-emptive-therapy-in-allogeneic-stem-cell-transplant-recipients
#9
Jose F Camargo, Erik Kimble, Rossana Rosa, Luis A Shimose, Maria X Bueno, Nikeshan Jeyakumar, Michele I Morris, Lilian M Abbo, Jacques Simkins, Maritza C Alencar, Cara Benjamin, Eric Wieder, Antonio Jimenez, Amer Beitinjaneh, Mark Goodman, John J Byrnes, Lazaros J Lekakis, Denise Pereira, Krishna V Komanduri
The optimal viral load threshold to initiate pre-emptive cytomegalovirus (CMV) therapy in hematopoietic cell transplant (HCT) recipients remains to be defined. In an effort to address this question we conducted a retrospective study of 174 allogeneic HCT recipients transplanted at a single center between August 2012 and April 2016. During this period, pre-emptive therapy started at the discretion of the treating clinician. 109 (63%) patients developed CMV viremia. Median time to reactivation was 17 (IQR, 7-30) days post-HCT...
December 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#10
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29209559/nkp46-expression-on-nk-cells-as-a-prognostic-and-predictive-biomarker-for-response-to-allo-sct-in-patients-with-aml
#11
Anne-Sophie Chretien, Raynier Devillier, Cyril Fauriat, Florence Orlanducci, Samia Harbi, Aude Le Roy, Jérôme Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Jean-François Hamel, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Christine Arnoulet, Norbert Vey, Didier Blaise, Daniel Olive
NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209333/inhibition-of-acute-graft-versus-host-disease-with-retention-of-graft-versus-tumor-effects-by-dimethyl-fumarate
#12
Jingjing Han, Shoubao Ma, Huanle Gong, Shuangzhu Liu, Lei Lei, Bo Hu, Yang Xu, Haiyan Liu, Depei Wu
Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29206745/cardiosphere-derived-cells-and-ischemic-heart-failure
#13
Carmel Ashur, William H Frishman
After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications...
January 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29205259/cd34-selected-stem-cell-boosts-can-improve-poor-graft-function-after-paediatric-allogeneic-stem-cell-transplantation
#14
Chiara Mainardi, Martin Ebinger, Sigrid Enkel, Tobias Feuchtinger, Heiko-Manuel Teltschik, Matthias Eyrich, Michael Schumm, Armin Rabsteyn, Patrick Schlegel, Christian Seitz, Carl-Phillip Schwarze, Ingo Müller, Johann Greil, Peter Bader, Paul-Gerhardt Schlegel, David Martin, Ursula Holzer, Michaela Döring, Rupert Handgretinger, Peter Lang
Poor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34+ selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n = 25) or mismatched related (n = 25) donors. Within 8 weeks, a significant increase in median neutrophil counts (0·6 vs. 1·516 × 109 /l, P < 0·05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs...
December 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29205184/adipose-derived-mesenchymal-stem-cells-suppress-of-acute-rejection-in-small-bowel-transplantation
#15
Yu Zhang, Qinghong Meng, Yanyan Zhang, Xiaobo Chen, Yuliang Wang
BACKGROUND/AIMS: Adipose-derived mesenchymal stem cells (ADSCs) possess immunosuppressive activity and hold promise in autologous cell-based therapies. The aim of this study was to determine whether autologous ADSCs can improve outcomes in the rat small bowel transplantation (SBT) model. MATERIALS AND METHODS: Allogeneic SBT followed by implantation of autologous ADSCs through the penile vein was conducted in Brown-Norway (BN) donor rats with Lewis (LEW) recipient rats infused with phosphate buffered solution as the control...
November 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/29204086/immunomodulatory-effect-of-moringa-peregrina-leaves-ex-vivo-and-in-vivo-study
#16
Ibrahim Salameh Al-Majali, Sawsan Atallah Al-Oran, Mona Rushdie Hassuneh, Haitham Naief Al-Qaralleh, Walid Abu Rayyan, Osama Yosef Al-Thunibat, Eyad Mallah, Ahmed Abu-Rayyan, Shadi Salem
This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/29200009/antifibrinolytic-therapy-and-perioperative-considerations
#17
Jerrold H Levy, Andreas Koster, Quintin J Quinones, Truman J Milling, Nigel S Key
Fibrinolysis is a physiologic component of hemostasis that functions to limit clot formation. However, after trauma or surgery, excessive fibrinolysis may contribute to coagulopathy, bleeding, and inflammatory responses. Antifibrinolytic agents are increasingly used to reduce bleeding, allogeneic blood administration, and adverse clinical outcomes. Tranexamic acid is the agent most extensively studied and used in most countries. This review will explore the role of fibrinolysis as a pathologic mechanism, review the different pharmacologic agents used to inhibit fibrinolysis, and focus on the role of tranexamic acid as a therapeutic agent to reduce bleeding in patients after surgery and trauma...
December 4, 2017: Anesthesiology
https://www.readbyqxmd.com/read/29197680/increased-co-expression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allo-sct
#18
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematological malignancy due to allo-reactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet, tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of co-stimulatory molecules and can up-regulate co-inhibitory molecules that, upon ligation with their counter receptors on the tumor-reactive T cells, inhibit T cell functionality...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29194581/hodgkin-lymphoma-a-review-and-update-on-recent-progress
#19
REVIEW
Satish Shanbhag, Richard F Ambinder
Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients...
December 1, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/29189896/between-a-rux-and-a-hard-place-evaluating-salvage-treatment-and-outcomes-in-myelofibrosis-after-ruxolitinib-discontinuation
#20
Andrew T Kuykendall, Savan Shah, Chetasi Talati, Najla Al Ali, Kendra Sweet, Eric Padron, David A Sallman, Jeffrey E Lancet, Alan F List, Kenneth S Zuckerman, Rami S Komrokji
Ruxolitinib is a JAK1/2 inhibitor that is effective in managing symptoms and splenomegaly related to myelofibrosis (MF). Unfortunately, many patients must discontinue ruxolitinib, at which time treatment options are not well defined. In this study, we investigated salvage treatment options and clinical outcomes among MF patients who received and discontinued ruxolitinib outside the context of a clinical trial. Among 145 patients who received ruxolitinib, 23 died while on treatment, 58 remained on treatment at time of analysis, leaving 64 people available for analysis...
November 30, 2017: Annals of Hematology
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