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Tregs, Leukemia

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https://www.readbyqxmd.com/read/29450641/chronic-lymphocytic-leukemia-cells-acquire-regulatory-b-cell-properties-in-response-to-tlr9-and-cd40-activation
#1
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...
February 15, 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
#2
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
#3
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...
February 6, 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
#4
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%...
February 2, 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
#5
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...
February 1, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-photosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28807569/il-10-engineered-human-cd4-tr1-cells-eliminate-myeloid-leukemia-in-an-hla-class-i-dependent-mechanism
#13
Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models...
October 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#14
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-regulatory-t-cells-prevent-graft-versus-host-disease-while-allowing-a-powerful-t-cell-dependent-graft-versus-leukemia-effect-in-murine-models
#15
Beatrice Del Papa, Loredana Ruggeri, Elena Urbani, Stefano Baldoni, Debora Cecchini, Tiziana Zei, Roberta Iacucci Ostini, Barbara Crescenzi, Alessandra Carotti, Antonio Pierini, Paolo Sportoletti, Paolo Di Bartolomeo, Franca Falzetti, Cristina Mecucci, Andrea Velardi, Massimo F Martelli, Mauro Di Ianni
We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#16
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
December 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#17
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
November 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#18
MULTICENTER STUDY
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28691927/ubiquitination-of-tumor-suppressor-pml-regulates-prometastatic-and-immunosuppressive-tumor-microenvironment
#19
Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 (CRL4WDR4)...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28679299/arsenic-trioxide-decreases-the-amount-and-inhibits-the-function-of-regulatory-t-cells-which-may-contribute-to-its-efficacy-in-the-treatment-of-acute-promyelocytic-leukemia
#20
Wen Xu, Xiaoxia Li, Lina Quan, Jiying Yao, Guannan Mu, Jingjie Guo, Yitong Wang
Arsenic trioxide (ATO) exhibits substantial clinical efficacy in the treatment of acute promyelocytic leukemia (APL). Here, we investigated whether ATO exerts its efficacy by affecting regulatory T (Treg) cells. We determined whether ATO treatment influenced the amount and function of purified Treg cells. We also examined the effect of ATO treatment on Treg cells from APL patients. ATO treatment induced apoptosis in purified Treg cells and dampened the inhibition of effector T (Teff) cells proliferation and the secretion of cytokine by Treg cells...
July 6, 2017: Leukemia & Lymphoma
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