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https://www.readbyqxmd.com/read/29790621/generation-and-application-of-human-induced-stem-cell-memory-t-it-scm-cells-for-adoptive-immunotherapy
#1
Taisuke Kondo, Yuuki Imura, Shunsuke Chikuma, Sana Hibino, Setsuko Omata-Mise, Makoto Ando, Takashi Akanuma, Mana Iizuka, Ryota Sakai, Rimpei Morita, Akihiko Yoshimura
Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming since TSCM cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29770133/peripheral-blood-stem-cell-mobilization-in-healthy-donors-by-granulocyte-colony-stimulating-factor-causes-preferential-mobilization-of-lymphocyte-subsets
#2
Guro Kristin Melve, Elisabeth Ersvaer, Geir Egil Eide, Einar K Kristoffersen, Øystein Bruserud
Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769201/in-vitro-priming-of-adoptively-transferred-t-cells-with-a-ror%C3%AE-agonist-confers-durable-memory-and-stemness-in-vivo
#3
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29765857/dna-methylation-and-adult-neurogenesis
#4
REVIEW
Emily M Jobe, Xinyu Zhao
The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29755666/impact-of-lenalidomide-maintenance-on-the-immune-environment-of-multiple-myeloma-patients-with-low-tumor-burden-after-autologous-stem-cell-transplantation
#5
Karel Fostier, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754771/epstein-barr-virus-specific-cytokine-induced-killer-cells-for-treatment-of-epstein-barr-virus-related-malignant-lymphoma
#6
Lisa-Marie Pfeffermann, Verena Pfirrmann, Sabine Huenecke, Melanie Bremm, Halvard Bonig, Hans-Michael Kvasnicka, Thomas Klingebiel, Peter Bader, Eva Rettinger
BACKGROUND: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context. METHODS: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool...
May 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29751848/differentiation-of-adipose-derived-stem-cells-into-schwann-cell-like-cells-through-intermittent-induction-potential-advantage-of-cellular-transient-memory-function
#7
Xun Sun, Yun Zhu, He-Yong Yin, Zhi-Yuan Guo, Feng Xu, Bo Xiao, Wen-Li Jiang, Wei-Min Guo, Hao-Ye Meng, Shi-Bi Lu, Yu Wang, Jiang Peng
BACKGROUND: Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29743350/high-throughput-sequencing-of-the-t-cell-receptor-%C3%AE-gene-identifies-aggressive-early-stage-mycosis-fungoides
#8
Adele de Masson, John T O'Malley, Christopher P Elco, Sarah S Garcia, Sherrie J Divito, Elizabeth L Lowry, Marianne Tawa, David C Fisher, Phillip M Devlin, Jessica E Teague, Nicole R Leboeuf, Ilan R Kirsch, Harlan Robins, Rachael A Clark, Thomas S Kupper
Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study...
May 9, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29740283/transplantation-of-human-menstrual-blood-derived-mesenchymal-stem-cells-alleviates-alzheimer-s-disease-like-pathology-in-app-ps1-transgenic-mice
#9
Yongjia Zhao, Xin Chen, Yichen Wu, Yanling Wang, Yifei Li, Charlie Xiang
Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer's disease (AD). Mesenchymal stem cells (MSCs) have shown therapeutic efficacy in many neurodegenerative diseases, including AD. Human menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs advantageous for their higher proliferation rate and because they are easy to obtain without ethical concerns. Although MenSCs have exhibited therapeutic efficacy in some diseases, their effects on AD remain elusive...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29726088/a-novel-2-phenylamino-quinazoline-based-compound-expands-the-neural-stem-cell-pool-and-promotes-the-hippocampal-neurogenesis-and-the-cognitive-ability-of-adult-mice
#10
Lu Hui, Cheng Gang, Hong Feng, Zhang Lei, Hu Youhong, Feng Linyin
The adult neurogenesis occurs throughout the life of the mammalian hippocampus and is found to be essential for learning and memory. Identifying new ways to manipulate the number of neural stem cells (NSCs) and enhance endogenous neurogenesis in adult is very important. Here we found that a novel compound, N2-(4-isopropylphenyl)-5-(3-methoxyphenoxy)quinazoline-2,4-diamine (code-named Yhhu-3792), enhanced the self-renewal capability of NSCs in vitro and in vivo. In vitro, Yhhu-3792 increased the ratio of BrdU + /DAPI+ embryonic NSCs and accelerated the growth of neurospheres significantly...
May 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29721391/a-genetic-ifn-stat1-fas-axis-determines-cd4-t-stem-cell-memory-levels-and-apoptosis-in-healthy-controls-and-adult-t-cell-leukemia-patients
#11
Ricardo Khouri, Gilvanéia Silva-Santos, Tim Dierckx, Soraya Maria Menezes, Daniele Decanine, Kristof Theys, Aline Clara Silva, Lourdes Farré, Achiléa Bittencourt, Massimo Mangino, Mario Roederer, Anne-Mieke Vandamme, Johan Van Weyenbergh
Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4+ CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM ) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29714500/cognitive-enhancement-of-volatile-oil-from-the-stems-of-schisandra-chinensis-baill-in-alzheimer-s-disease-rats
#12
Bingyou Yang, Bo Liu, Yan Liu, Hua Han, Haixue Kuang
The volatile oil (VO), extracted from the stems of Schisandra chinensis Baill. (SCS), was separated and identified by gas chromatography - mass spectrometry. The study was devised to investigate the effects of VO on oxidative stress and cognitive deficits induced by amyloid-β (Aβ(1-42)). Alzheimer's disease (AD) models were established by injecting Aβ(1-42) into the rat hippocampus and the effects of learning and memory were observed by a Morris water maze test, immunohistological alterations, and correlative indicators covering nerve growth (brain-derived neurotrophic factor, glial-cell-derived trophic factor, and nerve growth factor), interleukin 1β, tumor necrosis factor, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), glial fibrillary acidic protein (GFAP), and microglial CD11b in AD rats...
May 1, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29692783/cytomegalovirus-specific-cd8-t-cells-with-different-t-cell-receptor-affinities-segregate-t-cell-phenotypes-and-correlate-with-chronic-graft-versus-host-disease-in-patients-post-hematopoietic-stem-cell-transplantation
#13
Thomas Poiret, Rebecca Axelsson-Robertson, Mats Remberger, Xiao-Hua Luo, Martin Rao, Anurupa Nagchowdhury, Anna Von Landenberg, Ingemar Ernberg, Olle Ringden, Markus Maeurer
Virus-specific T-cell responses are crucial to control cytomegalovirus (CMV) infections/reactivation in immunocompromised individuals. Adoptive cellular therapy with CMV-specific T-cells has become a viable treatment option. High-affinity anti-viral cellular immune responses are associated with improved long-term immune protection against CMV infection. To date, the characterization of high-affinity T-cell responses against CMV has not been achieved in blood from patients after allogeneic hematopoietic stem cell transplantation (HSCT)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686714/current-perspectives-regarding-stem-cell-based-therapy-for-alzheimer-s-disease
#14
REVIEW
Kyeong-Ah Kwak, Seung-Pyo Lee, Jin-Young Yang, Young-Seok Park
Alzheimer's disease (AD), a progressive neurodegenerative disorder featuring memory loss and cognitive impairment, is caused by synaptic failure and the excessive accumulation of misfolded proteins. Many unsuccessful attempts have been made to develop new small molecules or antibodies to intervene in the disease's pathogenesis. Stem cell-based therapies cast a new hope for AD treatment as a replacement or regeneration strategy. The results from recent preclinical studies regarding stem cell-based therapies are promising...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29679650/cmv-seronegative-donors-effect-on-clinical-severity-of-cmv-infection-and-reconstitution-of-cmv-specific-immunity
#15
P L J van der Heiden, H M van Egmond, S A J Veld, M van de Meent, M Eefting, L C de Wreede, C J M Halkes, J H F Falkenburg, W A F Marijt, I Jedema
BACKGROUND: Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R+ D- ) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft. METHODS: We analyzed the duration of CMV reactivations and the incidence of CMV disease in R+ D- and R+ D+ patients after alemtuzumab-based T-cell depleted allogeneic stem cell transplantation (TCD alloSCT)...
April 18, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29678638/comprehensive-analysis-of-the-activation-and-proliferation-kinetics-and-effector-functions-of-human-lymphocytes-and-antigen-presentation-capacity-of-antigen-presenting-cells-in-xenogeneic-graft-versus-host-disease
#16
Yasufumi Kawasaki, Kazuya Sato, Hiroko Hayakawa, Norihito Takayama, Hirofumi Nakano, Ryoji Ito, Kiyomi Mashima, Iekuni Oh, Daisuke Minakata, Ryoko Yamasaki, Kaoru Morita, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Shin-Ichiro Fujiwara, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4+ and CD8+ T-cells, and donor/host hematopoietic and non-hematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T-cells and the antigen presentation capacity of donor/host hematopoietic and non-hematopoietic APCs in xenogeneic GVHD models using NOD/Shi-scid-IL2rgnull (NOG) mice...
April 17, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29670286/pluripotency-factors-functionally-premark-cell-type-restricted-enhancers-in-es-cells
#17
Hong Sook Kim, Yuliang Tan, Wubin Ma, Daria Merkurjev, Eugin Destici, Qi Ma, Tom Suter, Kenneth Ohgi, Meyer Friedman, Dorota Skowronska-Krawczyk, Michael G Rosenfeld
Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3 , but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29668078/adherence-and-immune-response-to-revaccination-following-hematopoietic-stem-cell-transplantation-at-a-pediatric-onco-hematology-reference-center
#18
Fernanda Gouveia-Alves, Roseane Gouveia, Valéria C Ginani, Adriana Seber, Danielle A Kuramoto, Gabriel F A Murad, Fernanda G Spina, Antonio S Petrilli, Victor G Zecchin, Celso Granato, Fabianne Carlesse, M Isabel de Moraes-Pinto
BACKGROUND: Revaccination after hematopoietic stem cell transplantation (HSCT) is necessary to compensate for the loss of immunological memory. The aims of this study were to evaluate the adherence to revaccination schedule and the humoral immune response to different vaccine antigens in HSCT pediatric and young adult patients. METHODS: Patients submitted to HSCT for over 3 years were recruited. After written informed consent, a questionnaire was filled in, the vaccination card was analyzed, a blood sample was collected and tested by ELISA for diphtheria, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, tetanus, measles, rubella and varicella antibodies...
April 18, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29664572/ilc2-memory-recollection-of-previous-activation
#19
REVIEW
Itziar Martinez-Gonzalez, Maryam Ghaedi, Catherine A Steer, Laura Mathä, Eric Vivier, Fumio Takei
Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29660266/role-of-stem-cell-like-memory-t-cells-in-systemic-lupus-erythematosus
#20
Ye Ji Lee, Ji Ah Park, Hyunmi Kwon, Youn Soo Choi, Kyeong Cheon Jung, Seong Hoe Park, Eun Bong Lee
OBJECTIVE: Stem cell-like memory T (TSCM ) cells are long-lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of TSCM cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify TSCM cells in patients suffering from systemic lupus erythematosus (SLE). METHODS: CD4+ and CD8+ TSCM cells were identified in SLE patients and healthy controls (HCs). In vitro culture systems, CD4+ TSCM cells were induced to differentiate into subsets of T cells, including follicular helper T (TFH ) cells and cytokine production pattern was measured after stimulation...
April 16, 2018: Arthritis & Rheumatology
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