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Th17 leukemia

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...
August 29, 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
Yongxia Wu, David Bastian, Steven Schutt, Hung Nguyen, Jianing Fu, Jessica Heinrichs, Changqing Xia, Xue-Zhong Yu
Graft-versus-host disease (GVHD), in both its acute (aGVHD) and chronic (cGVHD) forms, remains a major obstacle impeding successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells, in particular pathogenic T helper (Th) 1 and Th17 subsets, are a driving force for the induction of GVHD. IL-12 and IL-23 cytokines share a common p40 subunit and play a critical role in driving Th1 differentiation and in stabilizing the Th17 phenotype, respectively. In our current study, we hypothesized that p40 is an essential cytokine in the development of GVHD...
July 2015: Biology of Blood and Marrow Transplantation
Satya P Singh, Hongwei H Zhang, Hsinyi Tsang, Paul J Gardina, Timothy G Myers, Vijayaraj Nagarajan, Chang Hoon Lee, Joshua M Farber
Th17 cells, which express the chemokine receptor CCR6, are implicated in many immune-mediated disorders, such as psoriasis and multiple sclerosis. We found that expression levels of CCR6 on human effector/memory CD4(+) T cells reflect a continuum of Th17 differentiation. By evaluating the transcriptome in cells with increasing CCR6, we detected progressive upregulation of ZBTB16, which encodes the broad complex, tramtrack, bric-à-brac-zinc finger transcription factor promyelocytic leukemia zinc finger protein (PLZF)...
May 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
M Levite
Dopamine, a principal neurotransmitter, deserves upgrading to 'NeuroImmunotransmitter' thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent activator of resting effector T cells (Teffs), via two independent ways: direct Teffs activation, and indirect Teffs activation by suppression of regulatory T cells (Tregs). The review covers the following findings: (i) T cells express functional dopamine receptors (DRs) D1R-D5R, but their level and function are dynamic and context-sensitive, (ii) DR membranal protein levels do not necessarily correlate with DR mRNA levels, (iii) different T cell types/subtypes have different DR levels and composition and different responses to dopamine, (iv) autoimmune and pro-inflammatory T cells and T cell leukaemia/lymphoma also express functional DRs, (v) dopamine (~10(-8) M) activates resting/naive Teffs (CD8(+) >CD4(+) ), (vi) dopamine affects Th1/Th2/Th17 differentiation, (vii) dopamine inhibits already activated Teffs (i...
January 2016: Acta Physiologica
Jing-Jing Yu, Gang Chen, Nan-Nan Pang, Xin-Hong Guo, Lei Wang, Fang Zhao, Ming-Fang Tan, Jian-Hua Qu
OBJECTIVE: This study was to investigate the mRNA expression of T-bet, GATA-3, ROR γt and Foxp3 mRNA in peripheral blood of patients with chronic lymphocytic leukemia (CLL) in different stages and explore their potential role in the pathogenesis and clinical diagnosis. METHODS: A total of 46 newly diagnosed and untreated patients with CLL was chosen as patient group, including 16 patients in the stage of Binet A, 15 in the stage of Binet B, and 15 in the stage of Binet C; 20 healthy persons were selected as controls...
February 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Yiming Zhong, Shuai Dong, Ethan Strattan, Li Ren, Jonathan P Butchar, Kelsey Thornton, Anjali Mishra, Pierluigi Porcu, J Michael Bradshaw, Angelina Bisconte, Timothy D Owens, Erik Verner, Ken A Brameld, Jens Oliver Funk, Ronald J Hill, Amy J Johnson, Jason A Dubovsky
Interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK or TXK) are essential mediators of intracellular signaling in both normal and neoplastic T-cells and natural killer (NK) cells. Thus, ITK and RLK inhibitors have therapeutic potential in a number of human autoimmune, inflammatory, and malignant diseases. Here we describe a novel ITK/RLK inhibitor, PRN694, which covalently binds to cysteine residues 442 of ITK and 350 of RLK and blocks kinase activity. Molecular modeling was utilized to design molecules that interact with cysteine while binding to the ATP binding site in the kinase domain...
March 6, 2015: Journal of Biological Chemistry
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