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Treg leukemia

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https://www.readbyqxmd.com/read/29900057/d-2-hydroxyglutarate-interferes-with-hif-1%C3%AE-stability-skewing-t-cell-metabolism-towards-oxidative-phosphorylation-and-impairing-th17-polarization
#1
Martin Böttcher, Kathrin Renner, Raffaela Berger, Kristin Mentz, Simone Thomas, Zugey Elizabeth Cardenas-Conejo, Katja Dettmer, Peter J Oefner, Andreas Mackensen, Marina Kreutz, Dimitrios Mougiakakos
D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. However, prognostic impact of IDH mutations and high D-2HG levels remains controversial and might depend on the overall mutational context. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29898383/foxp3-positive-t-cell-lymphomas-in-non-htlv1-carriers-include-alk-negative-anaplastic-large-cell-lymphoma-expanding-the-spectrum-of-t-cell-lymphomas-with-regulatory-phenotype
#2
Cristiane R Ferreira, Shuchun Zhao, Malaya K Sahoo, Benjamin Pinsky, Jenna Weber, Luis A P C Lage, Juliana Pereira, Maria C N Zerbini, Yasodha Natkunam
Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining...
June 10, 2018: Human Pathology
https://www.readbyqxmd.com/read/29875319/phosphoinositide-3-kinase-%C3%AE-inhibition-promotes-antitumor-responses-but-antagonizes-checkpoint-inhibitors
#3
Ee Lyn Lim, Fiorella M Cugliandolo, Dalya R Rosner, David Gyori, Rahul Roychoudhuri, Klaus Okkenhaug
Multiple modes of immunosuppression restrain immune function within tumors. We previously reported that phosphoinositide 3-kinase δ (PI3Kδ) inactivation in mice confers resistance to a range of tumor models by disrupting immunosuppression mediated by regulatory T cells (Tregs). The PI3Kδ inhibitor idelalisib has proven highly effective in the clinical treatment of chronic lymphocytic leukemia and the potential to extend the use of PI3Kδ inhibitors to nonhematological cancers is being evaluated. In this work, we demonstrate that the antitumor effect of PI3Kδ inactivation is primarily mediated through the disruption of Treg function, and correlates with tumor dependence on Treg immunosuppression...
June 7, 2018: JCI Insight
https://www.readbyqxmd.com/read/29843224/up-regulation-of-regulatory-t-cells-cd200-and-tim3-expression-in-cytogenetically-normal-acute-myeloid-leukemia
#4
Asmaa M Zahran, Mostafa F Mohammed Saleh, Mona M Sayed, Amal Rayan, Arwa Mohammed Ali, Helal Hetta
BACKGROUND: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact. PATIENTS AND METHODS: This study included 40 patients with de novo AML-NC and 20 healthy controls...
May 15, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29803792/a-novel-fusion-protein-attenuates-collagen-induced-arthritis-by-targeting-interleukin-17a-and-tumor-necrosis-factor-%C3%AE
#5
Zhihang Liu, Liying Song, Yunxin Wang, Pengfei Xu, Xiaochen Guo, Jiarui Yang, Han Liu, Yuyang Wang, Chao Wu, Teng Zhang, Dan Yu, Yeboah Kwaku Opoku, Mir Hassan Khoso, Guiping Ren, Deshan Li
This study was undertaken to generate a novel dual targeting fusion protein (DTF), targeting tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A), and determine its anti-arthritis properties in vitro and in vivo. DTF consisted of an anti-IL-17A single chain variable fragment, a soluble TNF receptor 1, and an Fc fragment. Both clinical and histopathological evaluations suggest that DTF and etanercept can ameliorate collagen induced arthritis. However, the arthritis severity score of DTF-treated mice was lower than that of etanercept-treated mice...
May 25, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29783736/revisiting-cd28-superagonist-tgn1412-as-potential-therapeutic-for-pediatric-b-cell-leukemia-a-review
#6
REVIEW
Katelyn E Brown
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg ) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell...
May 19, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29743403/-role-of-anti-ccr4-antibody-in-the-treatment-of-transplant-eligible-patients-with-aggressive-adult-t-cell-leukemia-lymphoma
#7
Shigeo Fuji
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29455107/helios-expression-in-regulatory-t-cells-promotes-immunosuppression-angiogenesis-and-the-growth-of-leukemia-cells-in-pediatric-acute-lymphoblastic-leukemia
#8
Xue Li, Dong Li, Xiaoyang Huang, Panpan Zhou, Qing Shi, Bing Zhang, Xiuli Ju
Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs...
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29450641/chronic-lymphocytic-leukemia-cells-acquire-regulatory-b-cell-properties-in-response-to-tlr9-and-cd40-activation
#9
Shimrit Ringelstein-Harlev, Irit Avivi, Mona Fanadka, Netanel A Horowitz, Tami Katz
Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia...
May 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29415756/fli1-haploinsufficient-dermal-fibroblasts-promote-skin-localized-transdifferentiation-of-th2-like-regulatory-t-cells
#10
Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Megumi Hirabayashi, Kouki Nakamura, Shunsuke Miura, Takashi Yamashita, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato
BACKGROUND: Friend leukemia virus integration 1 (Fli1) deficiency, a predisposing factor of systemic sclerosis (SSc), induces SSc-like phenotypes in various cell types. A recent study demonstrated the transdifferentiation of T helper type 2 cell (Th2)-like regulatory T cells (Tregs) in SSc lesional skin through interleukin (IL)-33 produced by fibroblasts. Therefore, we investigated the role of Fli1 deficiency in dermal fibroblast-mediated transdifferentiation of Tregs. METHODS: Cytokine expression was assessed in Tregs by flow cytometry and in skin samples and cultivated cells by immunostaining, immunoblotting, and/or qRT-PCR...
February 7, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29408212/interaction-between-the-immune-system-and-acute-myeloid-leukemia-a-model-incorporating-promotion-of-regulatory-t-cell-expansion-by-leukemic-cells
#11
Yoshiaki Nishiyama, Yutaka Saikawa, Nobuaki Nishiyama
Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes...
March 2018: Bio Systems
https://www.readbyqxmd.com/read/29407585/regulatory-t-cell-inhibition-by-dasatinib-is-associated-with-natural-killer-cell-differentiation-and-a-favorable-molecular-response-the-final-results-of-the-d-first-study
#12
Yuho Najima, Chikashi Yoshida, Noriyoshi Iriyama, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
We evaluated the effects of regulatory T cell (Treg) inhibition during dasatinib treatment on the anticancer immune response, particularly on natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Fifty-two newly diagnosed Japanese patients with chronic myeloid leukemia (CML) in the chronic phase were enrolled in the D-first study; all received 100 mg of dasatinib once daily and were followed for at least 36 months. The cumulative deep molecular response (DMR, MR4) rate was 65% by 36 months; the 3-year overall survival was 96%...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29388481/chemotherapy-alters-the-increased-numbers-of-myeloid-derived-suppressor-and-regulatory-t-cells-in-children-with-acute-lymphoblastic-leukemia
#13
Mohamed Labib Salem, Mohamed R El-Shanshory, Said H Abdou, Mohamed S Attia, Shymaa M Sobhy, Mona F Zidan, Abdel-Aziz A Zidan
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs ) which we and others have reported to mediate suppression of anti-tumor immune responses. AIM: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients...
April 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-photosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#14
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29209333/inhibition-of-acute-graft-versus-host-disease-with-retention-of-graft-versus-tumor-effects-by-dimethyl-fumarate
#15
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/29202792/the-cc-chemokine-ligand-ccl-1-upregulated-by-the-viral-transactivator-tax-can-be-downregulated-by-minocycline-possible-implications-for-long-term-treatment-of-htlv-1-associated-myelopathy-tropical-spastic-paraparesis
#16
Mineki Saito, Hiroe Sejima, Tadasuke Naito, Hiroshi Ushirogawa, Toshio Matsuzaki, Eiji Matsuura, Yuetsu Tanaka, Tatsufumi Nakamura, Hiroshi Takashima
BACKGROUND: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
December 4, 2017: Virology Journal
https://www.readbyqxmd.com/read/29191842/targeting-the-anion-exchanger-2-with-specific-peptides-as-a-new-therapeutic-approach-in-b-lymphoid-neoplasms
#17
Jon Celay, Teresa Lozano, Axel R Concepcion, Elena Beltrán, Francesc Rudilla, María José García-Barchino, Eloy F Robles, Obdulia Rabal, Irene de Miguel, Carlos Panizo, Noelia Casares, Julen Oyarzabal, Jesús Prieto, Juan F Medina, Juan José Lasarte, José Ángel Martínez-Climent
Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition of their function appears as a promising immunotherapeuticimmunotherapy therapeutic approach in cancer patients. Mice with targeted deletion of the gene encoding the Cl-HCO3-anion exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in intracellular pH regulation, showed a progressive decrease in the number of Treg cells. We therefore challenged AE2 as a potential target for tumor immune therapy, and generated linear peptides designed to bind the third extracellular loop of AE2, which is crucial for its exchange activity...
November 30, 2017: Haematologica
https://www.readbyqxmd.com/read/29123956/mutations-in-jak2-and-calreticulin-genes-are-associated-with-specific-alterations-of-the-immune-system-in-myelofibrosis
#18
Marco Romano, Daria Sollazzo, Sara Trabanelli, Martina Barone, Nicola Polverelli, Margherita Perricone, Dorian Forte, Simona Luatti, Michele Cavo, Nicola Vianelli, Camilla Jandus, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2(V617F) ,13 exon-9 CALR mutation and 5 triple negative)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28944837/role-of-pim2-in-allergic-asthma
#19
Wei Du, Tiantian Chen, Yingmeng Ni, Xiaoxia Hou, Youchao Yu, Qi Zhou, Fang Wu, Wei Tang, Guochao Shi
T cell‑associated inflammation, particularly type 2 inflammation, has an important role in asthma pathogenesis, which is suppressed by regulatory T cells (Tregs). Proviral integration site for Moloney murine leukemia virus 2 (PIM2), a member off the serine/threonine kinase family, promotes the growth and survival of T cells and influences the function of Treg cells. However, whether PIM2 affects asthma pathogenesis remains unclear. Peripheral blood mononuclear cells and Treg cells from asthmatic and healthy subjects were obtained, and the expression level of PIM2 was measured by reverse transcription‑quantitative polymerase chain reaction and immunocytochemistry...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#20
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
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