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Tregs, Leukemia

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https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#1
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28257976/the-pbx1-lupus-susceptibility-gene-regulates-cd44-expression
#2
Yuxin Niu, Mayami Sengupta, Anton A Titov, Seung-Chul Choi, Laurence Morel
PBX1-d is novel splice isoform of pre-B-cell leukemia homeobox 1 (PBX1) that lacks its DNA-binding and Hox-binding domains, and functions as a dominant negative. We have shown that PBX1-d expression in CD4(+) T cells is associated with systemic lupus erythematosus (SLE) in a mouse model as well as in human subjects. More specifically, PBX1-d expression leads to the production of autoreactive activated CD4+ T cells, a reduced frequency and function of Foxp3+ regulatory T (Treg) cells and an expansion of follicular helper T (Tfh) cells...
February 28, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#3
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28167485/expression-of-th17-and-cd4-cd25-t-regulatory-cells-in-peripheral-blood-of-acute-leukemia-patients-and-their-prognostic-significance
#4
Mingli Xiang, Li Guo, Yan Ma, Yi Li
To discuss the expression of T helper cell 17 (Th17) cells and CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in peripheral blood (PB) of patients with acute leukemia (AL), and to explore the relationship between them and disease prognosis. 40 patients diagnosed with acute leukemia in The First Affiliated Hospital of Zhengzhou University from July 2012 to August 2014 were selected as the observation group. Meanwhile, 40 healthy people were taken as the control group. Flow Cytometry Method (FCM) was used to detect the level of Th17 cells and CD4(+) CD25(+) Foxp3(+) cells in peripheral blood of the two groups, and enzyme-linked immuno sorbent assay (ELISA) method was used to test the level of IL17 and TGF-β in peripheral blood of two groups; reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze the mRNA levels of RORγT and Foxp3 in peripheral blood...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28119525/frequency-of-regulatory-t-cells-determines-the-outcome-of-the-t-cell-engaging-antibody-blinatumomab-in-patients-with-b-precursor-all
#5
J Duell, M Dittrich, T Bedke, T Mueller, F Eisele, A Rosenwald, L Rasche, E Hartmann, T Dandekar, H Einsele, M S Topp
Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28088964/-the-influence-of-depression-degree-on-regulatory-t-cells-in-patients-with-non-m3-acute-myeloid-leukemia
#6
J Cao, B Yuan, P X Guo, H Q Zhu, Z Z Huang, Y He, Q Ding, Z Z Feng
Objective: To investigate the influence of depression levels on regulatory T cells (Tregs) in patients with non-M3 acute myeloid leukemia (AML). Methods: A total of 63 patients with primarily diagnostic non-M3 AML and 25 healthy controls were enrolled, and the levels of depression by using HADM score and the percentages of Tregs by flow cytometry were evaluated in pre-treatment and post-treatment, respectively. Results: After every course of chemotherapy, the percentages of Tregs of PBMNC in AML showed the higher level of (6...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-and-decreased-pd-1-and-immune-suppressors
#7
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n = 8), MMR (BCR-ABL1 ≤0.1%, n = 20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n = 16), and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n = 13)...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/27999757/ccl22-specific-t-cells-modulating-the-immunosuppressive-tumor-microenvironment
#8
Evelina Martinenaite, Shamaila Munir Ahmad, Morten Hansen, Özcan Met, Marie Wulff Westergaard, Stine Kiaer Larsen, Tobias Wirenfeldt Klausen, Marco Donia, Inge Marie Svane, Mads Hald Andersen
Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27868052/friend-or-foe-mogamulizumab-in-allogeneic-hematopoietic-stem-cell-transplantation-for-adult-t-cell-leukemia-lymphoma
#9
REVIEW
Shigeo Fuji, Takero Shindo
Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27722210/regulatory-t-cell-therapy-for-graft-versus-host-disease
#10
Jessica Heinrichs, David Bastian, Anandharaman Veerapathran, Claudio Anasetti, Brain Betts, Xue-Zhong Yu
Graft-versus-host disease (GVHD) is a significant cause of non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Existing strategies to prevent and treat GVHD are incomplete, where a significant portion of allo-HCT recipients developed this complication. Despite this, one such therapy has emerged involving the use of regulatory T cells (Tregs) to control GVHD. The use of natural Tregs (nTregs) yielded positive pre-clinical results and are actively under investigation to reduce GVHD...
2016: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/27707998/g-csf-induced-suppressor-il-10-neutrophils-promote-regulatory-t-cells-that-inhibit-graft-versus-host-disease-in-a-long-lasting-and-specific-way
#11
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27584054/increased-il-10-il-17-ratio-is-aggravated-along-with-the-prognosis-of-patients-with-chronic-lymphocytic-leukemia
#12
Nannan Pang, Rui Zhang, Jinhua Li, Zhenghao Zhang, Hailong Yuan, Gang Chen, Fang Zhao, Lei Wang, Haizhou Cao, Jianhua Qu, Jianbing Ding
OBJECTIVE: This study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL). METHODS: Totally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27573760/successful-treatment-with-mogamulizumab-followed-by-allogeneic-hematopoietic-stem-cell-transplantation-in-adult-t-cell-leukemia-lymphoma-a-report-of-two-cases
#13
Yukie Tsubokura, Atsushi Satake, Masaaki Hotta, Hideaki Yoshimura, Shinya Fujita, Yoshiko Azuma, Takahisa Nakanishi, Aya Nakaya, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura
A humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab (MOG), has been shown to be safe and effective in the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL). MOG depletes ATLL cells as well as regulatory T cells (Tregs), as CCR4 is expressed on these cells as well. In this context, pretransplant treatment with MOG may induce severe graft-versus-host disease (GVHD) in allogeneic hematopoietic stem-cell transplantation (HSCT). However, the influence of MOG on allogeneic HSCT, including its induction of GVHD, is unclear...
December 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27507878/pretransplantation-anti-ccr4-antibody-mogamulizumab-against-adult-t-cell-leukemia-lymphoma-is-associated-with-significantly-increased-risks-of-severe-and-corticosteroid-refractory-graft-versus-host-disease-nonrelapse-mortality-and-overall-mortality
#14
Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27505705/phase-i-study-of-azacitidine-following-donor-lymphocyte-infusion-for-relapsed-acute-myeloid-leukemia-post-allogeneic-stem-cell-transplantation
#15
Armin Ghobadi, Jaebok Choi, Mark A Fiala, Theresa Fletcher, Jingxia Liu, Linda G Eissenberg, Camille Abboud, Amanda Cashen, Ravi Vij, Mark A Schroeder, Iskra Pusic, Keith Stockerl-Goldstein, Meagan Jacoby, Geoffrey Uy, John DiPersio, Peter Westervelt
Donor lymphocyte infusion (DLI) without prophylactic immunosuppression has been used for relapsed AML after allogeneic stem cell transplant (allo-SCT). However DLI is associated with an increased incidence of acute Graft vs. Host Disease (aGVHD). In mice, administration of azacitidine (AzaC) on days 4, 6, 8, and 10 post DLI increases regulatory T cell (Treg) numbers and prevents GVHD without hindering Graft vs. Leukemia (GVL). Based on these findings, we conducted a phase 1 study of AzaC post DLI for AML relapse post allo-SCT...
October 2016: Leukemia Research
https://www.readbyqxmd.com/read/27471614/cd8-tregs-promote-gvhd-prevention-and-overcome-the-impaired-gvl-effect-mediated-by-cd4-tregs-in-mice
#16
Jessica Heinrichs, Jun Li, Hung Nguyen, Yongxia Wu, David Bastian, Anusara Daethanasanmak, M-Hanief Sofi, Steven Schutt, Chen Liu, Junfei Jin, Brian Betts, Claudio Anasetti, Xue-Zhong Yu
Adoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (Allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemia (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4(+) or CD8(+) T cells and tested their ability to suppress GVH and maintain GVL responses...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27401140/adenosine-selectively-depletes-alloreactive-t-cells-to-prevent-gvhd-while-conserving-immunity-to-viruses-and-leukemia
#17
Greg D Whitehill, Shoba Amarnath, Pawel Muranski, Keyvan Keyvanfar, Minoo Battiwalla, Austin J Barrett, Dhanalakshmi Chinnassamy
Selective depletion (SD) of alloreactive T cells from allogeneic hematopoeitic stem cell transplants to prevent graft-versus-host disease (GVHD) without compromising immune reconstitution and antitumor responses remains a challenge. Here, we demonstrate a novel SD strategy whereby alloreacting T cells are efficiently deleted ex vivo with adenosine. SD was achieved in human leukocyte antigen (HLA) mismatched cocultures by multiple exposures to 2 mmol/l adenosine over 7 days. Adenosine depleted greater than to 90% of alloproliferating T cells in mismatched, haploidentical, and matched sibling pairs while conserving response to third-party antigens...
September 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27354021/a-phase-i-study-of-cd25-regulatory-t-cell-depleted-donor-lymphocyte-infusion-for-relapse-after-allogeneic-stem-cell-transplantation
#18
Sarah Nikiforow, Haesook T Kim, Heather Daley, Carol Reynolds, Kyle Thomas Jones, Philippe Armand, Vincent T Ho, Edwin P Alyea, Corey S Cutler, Jerome Ritz, Joseph H Antin, Robert J Soiffer, John Koreth
Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Tregs) that may suppress graft-versus-tumor responses. We undertook a Phase I study of donor lymphocyte infusion depleted of CD25+ T cells in hematologic malignancies relapsed after transplantation. Twenty-one subjects received CD25/Treg-depleted infusion following removal of CD25+ cells using antibody-conjugated magnetic beads...
June 27, 2016: Haematologica
https://www.readbyqxmd.com/read/27338100/t-cell-defect-in-diffuse-large-b-cell-lymphomas-involves-expansion-of-myeloid-derived-suppressor-cells
#19
Imane Azzaoui, Fabrice Uhel, Delphine Rossille, Celine Pangault, Joelle Dulong, Jerome Le Priol, Thierry Lamy, Roch Houot, Steven Le Gouill, Guillaume Cartron, Pascal Godmer, Krimo Bouabdallah, Noel Milpied, Gandhi Damaj, Karin Tarte, Thierry Fest, Mikael Roussel
In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear...
August 25, 2016: Blood
https://www.readbyqxmd.com/read/27307158/hydroquinone-induced-foxp3-adam17-lyn-akt-p21-signaling-axis-promotes-malignant-progression-of-human-leukemia-u937-cells
#20
Ying-Jung Chen, Wen-Hsin Liu, Long-Sen Chang
Hydroquinone (1,4-benzenediol; HQ), a major marrow metabolite of the leukemogen benzene, has been proven to evoke benzene-related hematological disorders and myelotoxicity in vitro and in vivo. The goal of the present study was to explore the role of FOXP3 in HQ-induced malignant progression of U937 human leukemia cells. U937 cells were treated with 5 μM HQ for 24 h, and the cells were re-suspended in serum-containing medium without HQ for 2 days. The same procedure was repeated three times, and the resulting U937/HQ cells were maintained in cultured medium containing 5 μM HQ...
February 2017: Archives of Toxicology
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