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Allo immunization

Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
Lambros Kordelas, Fabiola da Silva Nardi, Bettina Wagner, Markus Ditschkowski, Tobias Liebregts, Monika Lindemann, Falko M Heinemann, Peter A Horn, Dietrich W Beelen, Vera Rebmann
HLA-G is a non-classical class I molecule which induces tolerance in allogeneic situations by inhibition of cytotoxic NK and CD8 + T cells and by induction of regulatory T cells. Concordantly, in solid organ transplantation HLA-G is associated with a lower risk for acute and chronic rejection, whereas its role in allogeneic stem cell transplantation (allo-SCT) is less established. We here present detailed analyses of HLA-G-levels in patients after allo-SCT showing a correlation of elevated soluble HLA-G (sHLA-G) levels with less severe acute (p = 0...
March 14, 2018: Bone Marrow Transplantation
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HCT). NK cells and γδ T cells reconstitute early after allo-HCT, contribute to tumor immunosurveillance via MHC independent mechanisms and do not induce graft-versus-host disease (GVHD). Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HCT (MSD/MUD-HCT) and umbilical cord blood-HCT (UCB-HCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
Gunjan L Shah, Craig H Moskowitz
The majority of patients with Hodgkin Lymphoma (HL) are cured with initial therapy. However, high dose therapy with autologous hematopoietic cell transplant (AHCT) allows for the cure of an additional portion of patients with relapsed or primary refractory disease (rrHL). PET negative complete remission (CR) prior to AHCT is critical for long-term disease control. Several salvage options are available with comparable response rates, and the choice can be dependent of comorbidities and logistics. Radiation therapy can also improve the remission rate and is an important therapeutic option for selected patients...
March 2, 2018: Blood
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
Yang Zhao, Xiao-Fei Shen, Ke Cao, Jie Ding, Xing Kang, Wen-Xian Guan, Yi-Tao Ding, Bao-Rui Liu, Jun-Feng Du
How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro . However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance...
2018: Frontiers in Immunology
François Huchet, Jean Christian Roussel, Vincent Letocart, Thibaut Manigold
AIMS: TAVR implantation in unicuspid aortic valve has rarely been reported previously, due to the rareness of this morphology. This case tries to bring answers to some challenges we may have to face in TAVR current practice. METHODS AND RESULTS: We describe the case of a cardiogenic shock complicating a pure native regurgitating and non-calcified unicuspid aortic valve, in a 40 years old woman without medical follow up. Conventional treatment options such as valve surgery or heart transplantation were denied due to extreme operative risk and multiple allo-immunizations...
February 27, 2018: EuroIntervention
Hung D Nguyen, Sandeepkumar Kuril, David Bastian, Xue-Zhong Yu
Metabolism, including catabolism and anabolism, is a basic cellular process necessary for cell survival. T lymphocytes have a distinct metabolism that can determine both fate and function. T-cell activation depends on glycolysis to obtain materials and energy for proliferation and effector function. Importantly, T cells utilize different metabolic processes under different conditions and diseases. Allogeneic hematopoietic cell transplantation (allo-HCT) is a classic immunotherapy for hematological malignancies; however, the development of graft-versus-host disease (GVHD) is a major factor limiting the success of allo-HCT...
2018: Frontiers in Immunology
Rizwan Romee, Sarah Cooley, Melissa M Berrien-Elliott, Peter Westervelt, Michael R Verneris, John E Wagner, Daniel J Weisdorf, Bruce R Blazar, Celalettin Ustun, Todd E DeFor, Sithara Vivek, Lindsey Peck, John F DiPersio, Amanda F Cashen, Rachel Kyllo, Amy Musiek, András Schaffer, Milan J Anadkat, Ilana Rosman, Daniel Miller, Jack O Egan, Emily K Jeng, Amy Rock, Hing C Wong, Todd A Fehniger, Jeffrey S Miller
New therapies for patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) are needed. Interleukin (IL)-15 is a cytokine that stimulates CD8+ T cell and NK cell anti-tumor responses, and we hypothesized this cytokine may augment anti-leukemia/lymphoma immunity in vivo. To test this, we performed a first-in-human multi-center phase 1 trial ( NCT01885897) of the IL-15 superagonist complex ALT-803 in patients who relapsed >60 days after allo-HCT...
February 20, 2018: Blood
Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C Robson, Paul S Frenette, Joji Fujisaki
A crucial player in immune regulation, FoxP3+ regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence...
February 7, 2018: Cell Stem Cell
Yusuke Shono, Marcel R M van den Brink
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer...
February 16, 2018: Nature Reviews. Cancer
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
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
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
Nataša Ilic, Alisa Gruden-Movsesijan, Jelena Cvetkovic, Sergej Tomic, Dragana Bozidar Vucevic, Carmen Aranzamendi, Miodrag Colic, Elena Pinelli, Ljiljana Sofronic-Milosavljevic
Trichinella spiralis, as well as its muscle larvae excretory-secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1...
2018: Frontiers in Immunology
Julia Suárez-González, Carolina Martínez-Laperche, Mi Kwon, Pascual Balsalobre, Diego Carbonell, María Chicano, Gabriela Rodríguez-Macías, David Serrano, Jorge Gayoso, José Luis Díez-Martín, Ismael Buño
Development of de novo hematological malignancies in donor cells following allogeneic stem cell transplantation provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed in order to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematological neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex-mismatch and conditioning regimen...
February 2, 2018: Biology of Blood and Marrow Transplantation
Moniek A de Witte, Jürgen Kuball, Jeffrey S Miller
Purpose of review: The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors which both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing Graft-versus-Host Disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis...
December 2017: Current Stem Cell Reports
Wei Du, Hemn Mohammadpour, Rachel E O'Neill, Sandeep Kumar, Chuan Chen, Michelle Qiu, Lin Mei, Jingxin Qiu, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage...
2018: Oncoimmunology
Brian C Betts, David Bastian, Supinya Iamsawat, Hung Nguyen, Jessica L Heinrichs, Yongxia Wu, Anusara Daenthanasanmak, Anandharaman Veerapathran, Alison O'Mahony, Kelly Walton, Jordan Reff, Pedro Horna, Elizabeth M Sagatys, Marie C Lee, Jack Singer, Ying-Jun Chang, Chen Liu, Joseph Pidala, Claudio Anasetti, Xue-Zhong Yu
Janus kinase 2 (JAK2) signal transduction is a critical mediator of the immune response. JAK2 is implicated in the onset of graft-versus-host disease (GVHD), which is a significant cause of transplant-related mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Transfer of JAK2-/- donor T cells to allogeneic recipients leads to attenuated GVHD yet maintains graft-versus-leukemia. Th1 differentiation among JAK2-/- T cells is significantly decreased compared with wild-type controls. Conversely, iTreg and Th2 polarization is significantly increased among JAK2-/- T cells...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
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