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https://www.readbyqxmd.com/read/28110394/chimeric-antigen-receptor-car-t-cells-lessons-learned-from-targeting-of-cd19-in-b-cell-malignancies
#1
Kevin A Hay, Cameron J Turtle
Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy...
January 21, 2017: Drugs
https://www.readbyqxmd.com/read/28110075/tlr9-mediated-regulatory-b10-cell-amplification-following-sub-total-body-irradiation-implications-in-attenuating-eae
#2
Jinsheng Hong, Jie Fang, Ruilong Lan, Qi Tan, Yeping Tian, Mei Zhang, Paul Okunieff, Lurong Zhang, Jianhua Lin, Deping Han
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%-3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9(-/-) mice...
January 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28109707/potential-risk-of-repeated-nasal-vaccination-that-induces-allergic-reaction-with-mucosal-ige-and-airway-eosinophilic-infiltration-in-cynomolgus-macaques-infected-with-h5n1-highly-pathogenic-avian-influenza-virus
#3
Misako Nakayama, Yasushi Itoh, Shintaro Shichinohe, Rumi Nakabayashi, Hirohito Ishigaki, Yoshihiro Sakoda, Quynh Mai Le, Yoshihiro Kawaoka, Hiroshi Kida, Kazumasa Ogasawara
The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28109284/development-of-plasmodium-falciparum-specific-na%C3%A3-ve-atypical-memory-and-plasma-b-cells-during-infancy-and-in-adults-in-an-endemic-area
#4
Allan Lugaajju, Sreenivasulu B Reddy, Mats Wahlgren, Fred Kironde, Kristina E M Persson
BACKGROUND: B-cells are essential in immunity against malaria, but which sub-sets of B-cells specifically recognize Plasmodium falciparum and when they appear is still largely unknown. RESULTS: Using the flow cytometry technique for detection of P. falciparum specific (Pf+) B-cells, this study for the first time measured the development of Pf+ B cell (CD19+) phenotypes in Ugandan babies from birth up to nine months, and in their mothers. The babies showed increases in Pf+ IgG memory B-cells (MBCs), atypical MBCs, and plasma cells/blasts over time, but the proportion of these cells were still lower than in the mothers who displayed stable levels (5, 18, and 3%, respectively)...
January 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28109153/-chemotherapy-increases-fc%C3%AE-riib-content-in-peripheral-blood-of-the-patients-with-lung-squamous-cell-carcinoma
#5
Jingjing Lu, Xiuqin Cao, Zhiwei Yang
Objective To detect the FcγRIIB content of monocytes and B cells, the concentration of soluble FcγRIIB (sFcγRIIB) and its antibodies in the peripheral blood of patients with lung squamous cell carcinoma (LSCC) before and after chemotherapy. Methods The expression and localization of FcγRIIB on monocytes and B cells were detected by immunofluorescence technique; the expression of FcγRIIB mRNA was examined by quantitative real-time PCR; Western blotting was performed to detect the expression of FcγRIIB protein; the serum concentrations of sFcγRIIB, sFcγRIIB-IgG complex, anti-FcγRIIB autoantibody were determined by ELISA...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28108610/circulating-cxcr5-pd-1-icos-follicular-t-helper-cells-are-increased-close-to-the-diagnosis-of-type-1-diabetes-in-children-with-multiple-autoantibodies
#6
Tyyne Viisanen, Emmi-Leena Ihantola, Kirsti Näntö-Salonen, Heikki Hyöty, Noora Nurminen, Jenni Selvenius, Auni Juutilainen, Leena Moilanen, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#7
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108506/biomarker-dynamics-in-b-cell-lymphoma-a-longitudinal-prospective-study-of-plasma-samples-up-to-25-years-before-diagnosis
#8
Florentin Späth, Carl Wibom, Esmeralda J M Krop, Ann-Sofie Johansson, Ingvar A Bergdahl, Roel Vermeulen, Beatrice Melin
The B-cell activation markers CXCL13, sCD23, sCD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of marker-disease association hampers interpretation. In this study, we identified 170 individuals who had donated two pre-diagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108486/regulation-of-the-immune-response-by-tgf-%C3%AE-from-conception-to-autoimmunity-and-infection
#9
Shomyseh Sanjabi, Soyoung A Oh, Ming O Li
Transforming growth factor β (TGF-β) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-β alters immunity under various conditions. Under steady-state conditions, TGF-β regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-β inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral (p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges...
January 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28108005/in-vitro-allogeneic-immune-cell-response-to-mesenchymal-stromal-cells-derived-from-human-adipose-in-patients-with-rheumatoid-arthritis
#10
P Usha Shalini, J V S Vidyasagar, Lakshmi Kumari Kona, Meenakshi Ponnana, Lakshmi Kiran Chelluri
We investigated the regulatory activity of human adipose-derived mesenchymal stromal cells (MSCs) (n=10) towards immune cells in a cohort of 84 rheumatoid arthritis (RA) patients, 36 apparently healthy controls. We co-cultured MSCs with lymphocyte subsets of T, B, and T regulatory cells (Tregs). Levels of the pro- and anti-inflammatory markers (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10)) were estimated in serum and co-culture supernatants. The study revealed a two-fold increase in the proportion of Tregs and an increased level of CD4(+)CD25(+)FoxP3...
January 12, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#11
Xiaohe Shen, Jizhao Yuan, Mengjie Zhang, Wenhua Li, Bing Ni, Yuzhang Wu, Li Jiang, Weiping Fan, Zhiqiang Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28107547/unusual-cohesive-growth-pattern-of-diffuse-large-b-cell-lymphoma-mimicking-metastatic-carcinoma
#12
Yingting Mok, Giap Hean Goh, Shi Wang
No abstract text is available yet for this article.
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28107482/a-circulating-microrna-signature-predicts-age-based-development-of-lymphoma
#13
Afshin Beheshti, Charles Vanderburg, J Tyson McDonald, Charusheila Ramkumar, Tatenda Kadungure, Hong Zhang, Ronald B Gartenhaus, Andrew M Evens
Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach...
2017: PloS One
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#14
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107431/characterization-of-a-broadly-reactive-anti-cd40-agonistic-monoclonal-antibody-for-potential-use-as-an-adjuvant
#15
Cameron Martin, Suryakant D Waghela, Shehnaz Lokhandwala, Andy Ambrus, Jocelyn Bray, Christina Vuong, Vanitha Vinodkumar, Paul J Dominowski, Sharath Rai, Duncan Mwangi, Dennis L Foss, Waithaka Mwangi
Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species...
2017: PloS One
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#16
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28107187/peripheral-blood-lymphocyte-to-monocyte-ratio-recovery-from-low-levels-at-diagnosis-after-completion-of-first-line-therapy-predicts-good-clinical-outcomes-in-patients-with-diffuse-large-b-cell-lymphoma
#17
Shujuan Zhou, Linglong Xu, Yongyong Ma, Liyuan Tang, Yu Zhang, Yifen Shi, Lan Sun, Yi Chen, Bin Liang, Yuhong Zhou, Kang Yu, Jianping Shen
We retrospectively analyzed LMR at diagnosis and at completion of first-line therapy and prognosis in173 patients with DLBCL from 2005 to 2016. We found that patients with an LMR < 3.2 at diagnosis, as well as at completion of first-line therapy, had significantly lower PFS and OS rates than those with an LMR ≥ 3.2 (P<0.05). Patients with LMR that recovered from the low level at diagnosis showed superior overall survival (OS) (P=0.000) and progression-free survival (PFS) (P=0.001) compared with patients who failed to achieve a higher value at the completion of therapy...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107180/identification-of-micrornas-implicated-in-the-late-differentiation-stages-of-normal-b-cells-suggests-a-central-role-for-mirna-targets-zeb1-and-tp53
#18
Giorgio Malpeli, Stefano Barbi, Simonetta Zupo, Gabriele Tosadori, Giovanni Scardoni, Anna Bertolaso, Silvia Sartoris, Stefano Ugel, Caterina Vicentini, Matteo Fassan, Annalisa Adamo, Mauro Krampera, Maria Teresa Scupoli, Carlo Maria Croce, Aldo Scarpa
In the late B cell differentiation stages, miRNAs expression modifications promoting or inhibiting key pathways are only partially defined. We isolated 29 CD19+ human B cell samples at different stages of differentiation: B cells from peripheral blood; naïve, germinal center (GC) and subepithelial (SE) B cells from tonsils. SE cells were further split in activated and resting B cell. The miRNA expression profile of these B cells was assessed by microarray analysis and selected miRNAs were validated by quantitative RT-PCR and in situ hybridization on normal tonsils...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106808/anti-fatigue-effects-of-the-unique-polysaccharide-marker-of-dendrobium-officinale-on-balb-c-mice
#19
Wei Wei, Zhi-Peng Li, Tong Zhu, Hau-Yee Fung, Tin-Long Wong, Xin Wen, Dik-Lung Ma, Chung-Hang Leung, Quan-Bin Han
Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106467/follicular-lymphoma-a-b-cell-malignancy-addicted-to-epigenetic-mutations
#20
Koorosh Korfi, Sara Ali, James A Heward, Jude Fitzgibbon
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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