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https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#1
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29320502/impaired-ifn-%C3%AE-mediated-signal-in-dendritic-cells-differentiates-active-from-latent-tuberculosis
#2
Stefania Parlato, Teresa Chiacchio, Debora Salerno, Linda Petrone, Luciano Castiello, Giulia Romagnoli, Irene Canini, Delia Goletti, Lucia Gabriele
Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD)...
2018: PloS One
https://www.readbyqxmd.com/read/29296749/high-cd123-levels-enhance-proliferation-in-response-to-il-3-but-reduce-chemotaxis-by-downregulating-cxcr4-expression
#3
Nicole L Wittwer, Gabriela Brumatti, Ceilidh Marchant, Jarrod J Sandow, Melanie K Pudney, Mara Dottore, Richard J D'Andrea, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29251166/expression-of-multiple-leukemic-stem-cell-markers-is-associated-with-poor-prognosis-in-de-novo-acute-myeloid-leukemia
#4
Tomohiro Yabushita, Hironaga Satake, Hayato Maruoka, Mari Morita, Daisuke Katoh, Yoshimitsu Shimomura, Satoshi Yoshioka, Takeshi Morimoto, Takayuki Ishikawa
Leukemic stem cells (LSCs) play a crucial role in chemotherapy resistance in acute myeloid leukemia (AML). Although the association between the expression of individual LSC markers and poor prognosis has been reported, few studies have evaluated the prognostic effect of multiple LSC markers in patients with AML. Herein, we examined three LSC markers (CD25, CD96, and CD123) and the combined effect of their expression on clinical outcome. We retrospectively analyzed 80 adult patients with de novo AML who received intensive chemotherapy...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29236355/b-cell-specific-protein-fcrla-is-expressed-by-plasmacytoid-dendritic-cells-in-humans
#5
Evdokiya Reshetnikova, Sergey Guselnikov, Olga Volkova, Konstantin Baranov, Alexander Taranin, Ludmila Mechetina
BACKGROUND: Fc receptor-like A (FCRLA) is a unique member of a family of Fc receptor like-molecules that lacks a transmembrane region and is an ER-resident protein. In mice and humans, FCRLA has been known as a B cell specific protein. We report here that, in humans, FCRLA is also expressed in a subpopulation of plasmacytoid dendritic cells (pDCs). METHODS: Human peripheral blood mononuclear cells (PBMC), splenocytes, and tonsillar cells were stained for lineage markers followed by fixation/saponin permeabilization and intracellular staining for FCRLA, and then analyzed by flow cytometry with CD123 and CD303 used as pDC markers...
December 13, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#6
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29189264/dendritic-cell-markers-and-pd-l1-are-expressed-in-mediastinal-gray-zone-lymphoma
#7
Kevin Pelland, Stephanie Mathews, Anitha Kamath, Paul Cohen, S David Hudnall, Claudiu V Cotta, Mina L Xu
AIMS: Mediastinal gray zone lymphoma (MGZL) is a rare entity with morphologic, immunophenotypic, and genetic features intermediate between classic Hodgkin lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). It is challenging to differentiate from CHL and PMBL. A specific dendritic cell gene expression profile can distinguish CHL and MGZL from PMBL. We hypothesized that the dendritic markers fascin and CD123 may be helpful in distinguishing MGZL from CHL and PMBL. We also investigated programmed death-ligand 1 (PD-L1) expression in MGZL, which may have therapeutic significance in this difficulty to treat tumor...
November 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29189162/tunneling-nanotubes-a-versatile-target-for-cancer-therapy
#8
Pragyaparamita Sahoo, Soumya Ranjan Jena, Luna Samanta
Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL) are common acute leukemia in adults and children respectively. In therapy process of these malignancies, chemotherapy is the main strategy that fails in many of cases. Moreover, chemotherapy is usually associated with adverse effects it also damages the healthy cells. In this regard, development of new therapies is essential. Monoclonal antibodies directed to the cell surface markers of leukemic blasts may have promising consequences. These tools can provide a specific cell targeting with minimal toxic effects on other normal cells...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29167990/histologic-analysis-has-a-prognostical-value-in-colorectal-biopsies-assessed-for-suspicion-of-graft-versus-host-disease
#9
Fanny Sauvestre, Geneviève Belleannée, Claire Bréal, Catherine Mohr, Harold IpKan Fong, Sébastien Cossin, Reza Tabrizi, Noël Milpied, Stéphane Vigouroux, Jean-François Goussot, Marion Marty
Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation, but clinical and histological features are unspecific. The aim of this study was to correlate the histological GI GVHD grade with the clinical outcomes. In a retrospective study of 112 patients with clinically suspected GI GVHD, colonic biopsies were reviewed by three pathologists without knowledge of the corresponding clinical data and classified in four scores, according to the NIH Consensus Project recommendations: no GVHD, possible, probable, and unequivocal GVHD...
November 22, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29166741/-the-study-of-expression-and-prognostic-value-of-cd123-in-acute-myeloid-leukemia-bone-marrow-blasts
#10
W Q Yue, G S Tang, M Liu, H Cheng, J Ding, T Wang, J M Wang, X X Hu, W P Zhang, L Chen, J M Yang
Objective: To study the expression of CD123 in bone marrow (BM) blasts of acute myeloid leukemia (AML) patients to explore the relationship between CD123 expression and therapeutic response and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD123 in BM blasts in 137 cases of newly diagnosed AML (excluded M(3)) , CD123 detected by flow cytometry≥20% was defined as positive, including 84 CD123(+) AML and 53 CD123(-) AML, efficacy and prognosis were compared between the two groups...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#11
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29137845/enumeration-of-bone-marrow-plasmacytoid-dendritic-cells-by-multiparameter-flow-cytometry-as-a-prognostic-marker-following-allogeneic-hematopoietic-stem-cell-transplantation
#12
Ruijun Jeanna Su, Ralph Green, Mingyi Chen
Plasmacytoid dendritic cells (pDCs) promote tolerance in solid organ transplants and hematopoietic stem cell transplantation (HSCT). pDCs originate from CD34(+) hematopoietic progenitors. Following allogeneic hematopoietic stem cell transplant (allo-HSCT), pDC reconstitution in the BM and PB gradually attain levels similar to those in healthy individuals. We have investigated the recovery of pDC following allo-HSCT as a means to predict successful marrow engraftment. We retrospectively studied immune reconstitution of pDC in the BM of 48 patients following allo-HSCT for initial diagnoses of leukemia or other malignancies...
October 31, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29136520/characterization-of-myeloid-cell-populations-in-human-testes-collected-after-sex-reassignment-surgery
#13
Rosalie Ponte, Franck P Dupuy, Fadi Brimo, Vikram Mehraj, Pierre Brassard, Maud Belanger, Ekaterina Yurchenko, Mohammad-Ali Jenabian, Nicole F Bernard, Jean-Pierre Routy
The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described. To overcome the challenges related to tissue sampling, we obtained testicular tissue from men under hormonal therapy who elected to have sex reassignment surgery (SRS)...
October 14, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29110361/hairy-cell-leukemia-2018-update-on-diagnosis-risk-stratification-and-treatment
#14
Xavier Troussard, Edouard Cornet
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation...
December 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29077054/development-of-a-chimeric-antigen-receptor-targeting-c-type-lectin-like-molecule-1-for-human-acute-myeloid-leukemia
#15
Eduardo Laborda, Magdalena Mazagova, Sida Shao, Xinxin Wang, Herlinda Quirino, Ashley K Woods, Eric N Hampton, David T Rodgers, Chan Hyuk Kim, Peter G Schultz, Travis S Young
The treatment of patients with acute myeloid leukemia (AML) with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR)-engineered T-cells (CAR-T-cells), a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29065396/cd34-cd38-cd123-cells-are-present-in-virtually-all-acute-myeloid-leukaemia-blasts-a-promising-single-unique-phenotype-for-minimal-residual-disease-detection
#16
Adhra Al-Mawali, Avinash Daniel Pinto, Shoaib Al-Zadjali
BACKGROUND/AIMS: In CD34-positive acute myeloid leukaemia (AML), the leukaemia-initiating event likely takes place in the CD34+CD38- cell compartment. CD123 has been shown to be a unique marker of leukaemic stem cells within the CD34+CD38- compartment. The aim of this study was to identify the percentage of CD34+CD38-CD123+ cells in AML blasts, AML CD34+CD38- stem cells, and normal and regenerating bone marrow CD34+CD38- stem cells from non-myeloid malignancies. METHODS: Thirty-eight adult de novo AML patients with intention to treat were enrolled after the application of inclusion criteria from February 2012 to February 2017...
October 25, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29064022/novel-pathways-and-potential-therapeutic-strategies-for-blastic-plasmacytoid-dendritic-cell-neoplasm-bpdcn-cd123-and-beyond
#17
REVIEW
Naveen Pemmaraju
No abstract text is available yet for this article.
December 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28986815/effects-of-compound-zhebei-granule-combined-with-doxorubicin-on-expression-of-specific-surface-antigens-in-mice-with-transplanted-kg-1a-cells
#18
Yu Zhang, Li Hou, Xin-Yi Chen
OBJECTIVE: To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells. METHODS: A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flanks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group...
October 6, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28967606/differentiation-of-human-dendritic-cell-subsets-for-immune-tolerance-induction
#19
N Deluce-Kakwata-Nkor, L Lamendour, V Chabot, A Héraud, Z Ivanovic, F Halary, F Dehaut, F Velge-Roussel
OBJECTIVES: Since no further progress was achieved, in order to improve the long-term organ transplantation outcome, the immune tolerance appears as an interesting therapeutic goal. Dendritic cells (DCs) are specialized cells participating in the homeostasis of the immune response. Moreover, subsets of DCs, identified in humans, appear to have their respective competences in immune response modulation. Our objective is to purify from PBMC or to differentiate DC subsets from monocytes using several strategies and evaluate their IL10 secretion...
September 26, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28954350/-clinical-characteristics-of-6-patients-with-blastic-plasmacytoid-dendritic-cell-neoplasm
#20
X Han, M Q Ouyang, Q Pei, M H Duan, X Y Jiang, D B Zhou
Objective: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm. Method: Clinical records of 6 patients diagnosed with blastic plasmacytoid dendritic cell neoplasm in our hospital from January 2008 to May 2016 were collected and retrospectively analyzed. Results: Six patients manifested with initial symptoms of skin lesions, other common symptoms included bone marrow involvement (5/6) , lymphadenectasis (4/6) , splenomegaly (4/6) , and hepatomegaly (3/6) ...
August 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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