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Th17 leukemia

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
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
Marzia Palma, Giusy Gentilcore, Kia Heimersson, Fariba Mozaffari, Barbro Näsman-Glaser, Emma Young, Richard Rosenquist, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T cell defects. T cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared to healthy controls...
December 7, 2016: Haematologica
Maria Winqvist, Fariba Mozaffari, Marzia Palma, Sandra Eketorp Sylvan, Lotta Hansson, Håkan Mellstedt, Anders Österborg, Jeanette Lundin
This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2...
January 2017: Cancer Immunology, Immunotherapy: CII
Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto
Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD...
October 2016: Acta Medica Okayama
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
Natali Pflug, Sandra Kluth, Jörg J Vehreschild, Jasmin Bahlo, Daniela Tacke, Lena Biehl, Barbara Eichhorst, Kirsten Fischer, Paula Cramer, Anna-Maria Fink, Michael von Bergwelt-Baildon, Stephan Stilgenbauer, Michael Hallek, Oliver A Cornely, Maria J G T Vehreschild
Reduced anticancer efficacy of cyclophosphamide and platinum salts has been reported in animals treated with anti-Gram-positive antibiotics. These effects were related to translocation of Gram-positive bacteria during mucositis with subsequent induction of cytotoxic oxygen reactive species and tumor invasion by pathogenic Th17 cells. To assess these hypotheses in a clinical setting, we identified patients receiving cyclophosphamide for chronic lymphocytic leukemia (CLL) and cisplatin for relapsed lymphoma. Data originated from the CLL8 trial (NCT00281918) and the Cologne Cohort of Neutropenic Patients (NCT01821456)...
June 2016: Oncoimmunology
Laixi Bi, Junqing Wu, Aifang Ye, Jianbo Wu, Kang Yu, Shenghui Zhang, Yixiang Han
BACKGROUND: Immune regulation is crucial for the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL). It has been reported that Th17 cells as a newly identified subset of CD4(+) T cells are involved in the pathogenesis of several hematological disorders. However, the role of Th17 cells in the pathophysiology of B-ALL is still unclear. METHODS: The frequencies of T cells were determined by flow cytometry in the peripheral blood and bone marrow of 44 newly diagnosed B-ALL patients and 25 age-matched healthy donors...
2016: Journal of Translational Medicine
Astrid Olsnes Kittang, Shahram Kordasti, Kristoffer Evebø Sand, Benedetta Costantini, Anne Marijn Kramer, Pilar Perezabellan, Thomas Seidl, Kristin Paulsen Rye, Karen Marie Hagen, Austin Kulasekararaj, Øystein Bruserud, Ghulam J Mufti
Although the role of CD4(+) T cells and in particular Tregs and Th17 cells is established in myelodysplastic syndrome(MDS), the contribution of other components of immune system is yet to be elucidated fully. In this study we investigated the number and function of myeloid derived suppressor cells (MDSCs) in fresh peripheral blood and matched bone marrow samples from 42 MDS patients and the potential correlation with risk of disease progression to acute myeloid leukemia (AML). In peripheral blood, very low-/low risk patients had significantly lower median MDSC number (0...
February 2016: Oncoimmunology
Laura Vela, Iván Caballero, Leiping Fang, Qin Liu, Fernando Ramón, Emilio Díez, Maite de Los Frailes
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that involves activation of T cells, microglia, and astrocytes. There is a clear unmet medical need for MS, as current therapies reduce the relapse rate, but are unable to prevent the neurological deterioration. Leukemia inhibitory factor (LIF) is a proinflammatory cytokine that can also positively modulate the immune response, by inducing the inhibition of myelin-reactive TH17 differentiation, and by promoting oligodendrocyte-mediated myelination...
June 2016: Journal of Biomolecular Screening
Carsten U Niemann, Sarah E M Herman, Irina Maric, Julio Gomez-Rodriguez, Angelique Biancotto, Betty Y Chang, Sabrina Martyr, Maryalice Stetler-Stevenson, Constance M Yuan, Katherine R Calvo, Raul C Braylan, Janet Valdez, Yuh Shan Lee, Deanna H Wong, Jade Jones, Clare Sun, Gerald E Marti, Mohammed Z H Farooqui, Adrian Wiestner
PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B-cell receptor (BCR) signaling. Ibrutinib, a Bruton tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. Although the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment...
April 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Barbara Sherry, Preetesh Jain, Pui Yan Chiu, Ling Leung, Steven L Allen, Jonathan E Kolitz, Kanti R Rai, Jacquie Barrientos, Spencer Liang, Rachael Hawtin, Nicholas Chiorazzi
Chronic lymphocytic leukemia (CLL) is characterized by a progressive accumulation of B lymphocytes. T cell abnormalities are a common feature of CLL and contribute to impaired immune function in these patients. T cells are ineffective in eliminating the leukemic clone and may actually promote tumor growth and survival. Previous work from our laboratory documented elevated circulating levels of IL-17A-producing Th17 cells in CLL patients as compared to healthy age-matched control subjects. These high circulating Th17 levels associated with better prognostic markers and significantly longer overall survival, even among patients whose clones used unmutated IGHVs (U-CLL)...
December 2015: Immunologic Research
R H Prabhala, M Fulciniti, D Pelluru, N Rashid, A Nigroiu, P Nanjappa, C Pai, S Lee, N S Prabhala, R L Bandi, R Smith, S B Lazo-Kallanian, S Valet, N Raje, J S Gold, P G Richardson, J F Daley, K C Anderson, S A Ettenberg, F Di Padova, N C Munshi
We have previously demonstrated that interleukin-17A (IL-17) producing T helper 17 cells are significantly elevated in blood and bone marrow (BM) in multiple myeloma (MM) and IL-17A promotes MM cell growth via the expression of IL-17 receptor. In this study, we evaluated anti-human IL-17A human monoclonal antibody (mAb), AIN457 in MM. We observe significant inhibition of MM cell growth by AIN457 both in the presence and the absence of BM stromal cells (BMSCs). Although IL-17A induces IL-6 production, AIN457 significantly downregulated IL-6 production and MM cell adhesion in MM-BMSC co-culture...
February 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Biao Zhu, Jianbo Zhang, Xiaodong Wang, Jiao Chen, Chenglong Li
Recent studies have shown that Th17 cells may be involved in the pathological process of acute myeloid leukemia. This CD4+ cell subgroup secretes highly homologous interleukin (IL)-17A and IL-17F, and also expresses IL-23 receptor (IL-23R) on the cell surface. Our study aims to investigate the relationship of IL-17A, IL-17F, and IL23R with disease susceptibility, and clarify the relationship between gene polymorphism variation and serum IL-17 level. 62 acute myeloid leukemia patients and 125 healthy controls were included in this study...
2015: International Journal of Clinical and Experimental Pathology
Jun Long, Li Chang, Yan Shen, Wen-Hui Gao, Yue-Nv Wu, Han-Bo Dou, Meng-Meng Huang, Ying Wang, Wei-Yue Fang, Jie-Hui Shan, Yue-Ying Wang, Jiang Zhu, Zhu Chen, Jiong Hu
Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation. Valproic acid (VPA) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models. Using well-characterized mouse models of MHC-mismatched transplantation, we studied the effects of VPA on GVHD severity and graft-versus-leukemia (GVL) activity. Administration of VPA significantly attenuated the clinical severity of GVHD, the histopathology of GVHD-involved organs, and the overall mortality from GVHD...
August 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Gerardo Musuraca, Serena De Matteis, Roberta Napolitano, Cristina Papayannidis, Viviana Guadagnuolo, Francesco Fabbri, Delia Cangini, Michela Ceccolini, Maria Benedetta Giannini, Alessandro Lucchesi, Sonia Ronconi, Paolo Mariotti, Paolo Savini, Monica Tani, Pier Paolo Fattori, Massimo Guidoboni, Giovanni Martinelli, Wainer Zoli, Dino Amadori, Silvia Carloni
BACKGROUND: Acute myeloid leukemia (AML) is an incurable disease with fatal infections or relapse being the main causes of death in most cases. In particular, the severe infections occurring in these patients before or during any treatment suggest an intrinsic alteration of the immune system. In this respect, IL-17-producing T helper (Th17) besides playing a key role in regulating inflammatory response, tumor growth and autoimmune diseases, have been shown to protect against bacterial and fungal pathogens...
2015: Journal of Translational Medicine
Tian Tian, Shuang Yu, Lu Liu, Fuzhong Xue, Cunzhong Yuan, Min Wang, Chunyan Ji, Daoxin Ma
BACKGROUND: T helper (Th) cells immune regulation is important for the pathogenesis of acute myeloid leukemia (AML). Recurrent Th abnormalities in AML peripheral blood were reported, while the comprehensive status of various Th subsets is rarely investigated in bone marrow (BM) microenvironment which is the origin of AML leukemic blast cells. METHODS: BM was extracted from 48 newly-diagnosed (ND), 34 complete-remission (CR), 19 relapsed-refractory AML patients and 15 controls...
2015: PloS One
Ping Chen, Min Wang, Daqi Li, Yan Jia, Na He, Wei Li, Daoxin Ma, Chunyan Ji
T helper- (Th-) cell immunodeficiency plays important roles in tumor development and their effects in chronic myeloid leukemia (CML) remain unclear. In the present study, we mainly investigated the role of Th22, Th17, and Th1 cell and their related cytokines (IL-22, IL-17, and IFN-r) in the pathophysiology of CML. Bone marrow (BM) and peripheral blood (PB) were extracted from newly diagnosed (ND), chronic phase- (CP-) CML patients, and controls. Th subsets were examined by flow cytometry. Plasma IL-22, IL-17, and IFN-r concentrations were measured by ELISA...
2015: Journal of Immunology Research
Byung Hyun Kang, Hyo Jin Park, Hye In Yum, Seung Pyo Park, Jin Kyun Park, Eun Ha Kang, Jae-Il Lee, Eun Bong Lee, Chung-Gyu Park, Kyeong Cheon Jung, Seong Hoe Park
Identification of intrathymic eomesodermin(+) (Eomes(+)) CD4 T cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. Promyelocytic leukemia zinc finger protein(+) T cells and natural Th17 cells are known to be generated by sensing a high and persistent TCR strength, whereas this is not the case for Eomes(+) CD4 T cells. These cells go through low-level signal during the entire maturation pathway, which subsequently leads to induction of high susceptibility to cytokine IL-4...
June 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Mehdi Yousefi, Ali Akbar Movassaghpour, Karim Shamsasenjan, Ghasem Ghalamfarsa, Sanam Sadreddini, Farhad Jadidi-Niaragh, Mohammad Hojjat-Farsangi
While Tregs maintain self-tolerance and inhibit antitumor responses, T helper (Th)17 cells may enhance inflammatory and antitumor responses. The balance between these two important T-cell subsets has been skewed in many immunopathologic conditions such as autoimmune and cancer diseases. B-cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western world and is characterized with monoclonal expansion of B lymphocytes. There is evidence which implies that the progression of CLL is associated with expansion of Treg and downregulation of Th17 cells...
2015: Future Oncology
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