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Myeloid regulatory cells

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https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#1
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#2
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#3
F Zhao, Y Shi, Y Huang, Y Zhan, L Zhou, Y Li, Y Wan, H Li, H Huang, H Ruan, L Luo, L Li
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28619754/antitumor-effect-of-the-atypical-retinoid-st1926-in-acute-myeloid-leukemia-and-nanoparticle-formulation-prolongs-lifespan-and-reduces-tumor-burden-of-xenograft-mice
#4
Leeanna El-Houjeiri, Walid Saad, Berthe Hayar, Patrick Aouad, Nadim Tawil, Rana Abdel-Samad, Rita Hleihel, Maguy Hamie, Angelo Mancinelli, Claudio Pisano, Hiba El Hajj, Nadine Darwiche
Acute myeloid leukemia (AML) is one of the most frequent types of blood malignancies. It is a complex disorder of undifferentiated hematopoietic progenitor cells. The majority of patients generally respond to intensive therapy. Nevertheless, relapse is the major cause of death in AML, warranting the need for novel treatment strategies. Retinoids have demonstrated potent differentiation and growth regulatory effects in normal, transformed and hematopoietic progenitor cells. All-trans retinoic acid (ATRA) is the paradigm of treatment in acute promyelocytic leukemia, an AML subtype...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28611288/an-aml1-eto-mir-29b-1-regulatory-circuit-modulates-phenotypic-properties-of-acute-myeloid-leukemia-cells
#5
Sayyed K Zaidi, Andrew W Perez, Elizabeth S White, Jane B Lian, Janet L Stein, Gary S Stein
Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607471/gemtuzumab-ozogamicin-in-acute-myeloid-leukemia
#6
REVIEW
C D Godwin, R P Gale, R B Walter
CD33 is variably expressed on leukemia blasts in almost all patients with acute myeloid leukemia (AML) and possibly leukemia stem cells in some. Efforts to target CD33 therapeutically have focused on gemtuzumab ozogamicin (GO; Mylotarg®), an antibody-drug conjugate delivering a DNA-damaging calicheamicin derivative. GO is most effective in acute promyelocytic leukemia but induces remissions in other AML types and received accelerated approval in the US in 2000. However, because a large follow-up study showed no survival improvement and increased early deaths the drug manufacturer voluntarily withdrew the US New Drug Application in 2010...
June 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28599274/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#7
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control.Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595538/immune-cells-act-as-promising-targets-for-the-treatment-of-bone-metastasis
#8
Guojing Luo, Yuedong He, Qian Zhao, Xijie Yu
BACKGROUND: Bone metastasis is a common complication of certain types of cancer, and unfortunately, it is still incurable to date. Immune system is a major defence against tumor cells and bone metastasis. However, the immunodeficient mouse models are widely used in most researches of bone metastasis, thereby excluding the regulatory roles of the immune system in bone metastasis. OBJECTIVE: To provide a comprehensive overview on the cellular and molecular mechanisms by which immune cells interact with tumor cells and bone cells, as well as recent related patents...
June 6, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28584128/bcl11b-and-combinatorial-resolution-of-cell-fate-in-the-t-cell-gene-regulatory-network
#9
William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg
T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28584084/logical-modeling-of-lymphoid-and-myeloid-cell-specification-and-transdifferentiation
#10
Samuel Collombet, Chris van Oevelen, Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di Stefano, Morgane Thomas-Chollier, Thomas Graf, Denis Thieffry
Blood cells are derived from a common set of hematopoietic stem cells, which differentiate into more specific progenitors of the myeloid and lymphoid lineages, ultimately leading to differentiated cells. This developmental process is controlled by a complex regulatory network involving cytokines and their receptors, transcription factors, and chromatin remodelers. Using public data and data from our own molecular genetic experiments (quantitative PCR, Western blot, EMSA) or genome-wide assays (RNA-sequencing, ChIP-sequencing), we have assembled a comprehensive regulatory network encompassing the main transcription factors and signaling components involved in myeloid and lymphoid development...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28579269/irf2-inpp4b-axis-participates-in-the-development-of-acute-myeloid-leukemia-by-regulating-cell-growth-and-survival
#11
Feng Zhang, Junfeng Zhu, Jiajia Li, Fangbing Zhu, Pingping Zhang
Acute myeloid leukemia (AML) is a highly heterogeneous disease, which results in the fact that patient management has remained disappointingly uniform. Therefore, the molecular mechanism underlying AML needs to be further investigated. Here in this study, we identify the interferon-regulatory factor 2 (IRF2) as a novel regulator in human AML. We show that IRF2 knockdown inhibits growth, colony formation of OCI/AML-2, OCI/AML-3, and THP-1 cells. In addition, IRF2 knockdown induces apoptosis of AML cells by regulating the apoptotic effectors Bcl-2, Bax and Caspase 3...
June 2, 2017: Gene
https://www.readbyqxmd.com/read/28578659/rapamycin-mtorc1-inhibitor-reduces-the-production-of-lactate-and-2-hydroxyglutarate-oncometabolites-in-idh1-mutant-fibrosarcoma-cells
#12
Zoltán Hujber, Gábor Petővári, Norbert Szoboszlai, Titanilla Dankó, Noémi Nagy, Csilla Kriston, Ildikó Krencz, Sándor Paku, Olivér Ozohanics, László Drahos, András Jeney, Anna Sebestyén
BACKGROUND: Multiple studies concluded that oncometabolites (e.g. D-2-hydroxyglutarate (2-HG) related to mutant isocitrate dehydrogenase 1/2 (IDH1/2) and lactate) have tumour promoting potential. Regulatory mechanisms implicated in the maintenance of oncometabolite production have great interest. mTOR (mammalian target of rapamycin) orchestrates different pathways, influences cellular growth and metabolism. Considering hyperactivation of mTOR in several malignancies, the question has been addressed whether mTOR operates through controlling of oncometabolite accumulation in metabolic reprogramming...
June 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28574651/impact-of-tobacco-smoke-on-upper-airway-dendritic-cell-accumulation-and-regulation-by-sinonasal-epithelial-cells
#13
Jennifer K Mulligan, Brendan P O'Connell, Whitney Pasquini, Ryan M Mulligan, Sarah Smith, Zachary M Soler, Carl Atkinson, Rodney J Schlosser
BACKGROUND: In these studies we examined the impact of environmental tobacco smoke (ETS) and active smoking on sinonasal dendritic cell (DC) subsets in controls or patients with chronic rhinosinusitis with nasal polyps (CRSwNP). In subsequent in-vitro investigations, we examined the influence of cigarette smoke extract (CSE) on human sinonasal epithelial cells' (HSNECs) ability to regulate DC functions. METHODS: Sinonasal tissue, blood, and hair were collected from patients undergoing sinus surgery...
June 2, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28557618/microenvironment-tumor-metabolic-interactions-highlighted-by-qmsi-application-to-the-tryptophan-kynurenine-pathway-in-immuno-oncology
#14
Rima Ait-Belkacem, Vanesa Bol, Gregory Hamm, Florence Schramme, Benoit Van Den Eynde, Lauranne Poncelet, Fabien Pamelard, Jonathan Stauber, Bruno Gomes
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28552407/a-novel-platform-for-immune-tolerance-induction-in-hemophilia-a-mice
#15
Simone Merlin, Elvira Stefania Cannizzo, Ester Borroni, Valentina Bruscaggin, Piercarla Schinco, Warut Tulalamba, Marinee K Chuah, Valder R Arruda, Thierry VandenDriessche, Maria Prat, Guido Valente, Antonia Follenzi
Hemophilia A (HA) is an X-linked bleeding disease caused by factor VIII (FVIII) deficiency. We previously demonstrated that FVIII is produced specifically in liver sinusoid endothelial cells (LSECs) and to some degree in myeloid cells, and thus, in the present work, we seek to restrict the expression of FVIII transgene to these cells using cell-specific promoters. With this approach, we aim to limit immune response in a mouse model by lentiviral vector (LV)-mediated gene therapy encoding FVIII. To increase the target specificity of FVIII expression, we included miRNA target sequences (miRTs) (i...
May 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28550414/dasatinib-rapidly-induces-deep-molecular-response-in-chronic-phase-chronic-myeloid-leukemia-patients-who-achieved-major-molecular-response-with-detectable-levels-of-bcr-abl1-transcripts-by-imatinib-therapy
#16
Masayuki Shiseki, Chikashi Yoshida, Naoki Takezako, Akira Ohwada, Takashi Kumagai, Kaichi Nishiwaki, Akira Horikoshi, Tetsuya Fukuda, Hina Takano, Yasuji Kouzai, Junji Tanaka, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
BACKGROUND: With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment...
May 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#17
Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D Ho, Christoph Lutz
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#18
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546500/myeloid-derived-suppressor-cells-a-new-therapeutic-target-to-overcome-resistance-to-cancer-immunotherapy
#19
REVIEW
Jason A Chesney, Robert A Mitchell, Kavitha Yaddanapudi
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. Despite some encouraging improvements in response rates and overall survival in patients receiving immunotherapies, such as immune checkpoint inhibitors, most patients will ultimately progress...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28533469/the-phenotype-and-function-of-myeloid-derived-suppressor-cells-induced-by-porphyromonas-gingivalis-infection
#20
Lingkai Su, Qingan Xu, Ping Zhang, Suzanne M Michalek, Jannet Katz
Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, has been reported to induce the expansion of myeloid-derived suppressor cells (MDSC); however, little is known regarding the subpopulations of MDSC expanded by Pg infection. Flow cytometry was used to evaluate bone marrow and spleen cells from mice infected with Pg and controls for surface expression of CD11b, Ly6G and Ly6C. To characterize the phenotype of MDSC subpopulations induced by infection, cells were sorted based on the differential expression of Ly6G and Ly6C...
May 22, 2017: Infection and Immunity
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