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Heather Wood
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October 21, 2016: Nature Reviews. Neurology
Xiaobo Mao, Michael Tianhao Ou, Senthilkumar S Karuppagounder, Tae-In Kam, Xiling Yin, Yulan Xiong, Preston Ge, George Essien Umanah, Saurav Brahmachari, Joo-Ho Shin, Ho Chul Kang, Jianmin Zhang, Jinchong Xu, Rong Chen, Hyejin Park, Shaida A Andrabi, Sung Ung Kang, Rafaella Araújo Gonçalves, Yu Liang, Shu Zhang, Chen Qi, Sharon Lam, James A Keiler, Joel Tyson, Donghoon Kim, Nikhil Panicker, Seung Pil Yun, Creg J Workman, Dario A A Vignali, Valina L Dawson, Han Seok Ko, Ted M Dawson
Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity...
September 30, 2016: Science
Qin Xu, Shuo Wang, Yuming Guo, Chao Wang, Fangfang Huang, Xia Li, Qi Gao, Lijuan Wu, Lixin Tao, Jin Guo, Wei Wang, Xiuhua Guo
Fine particulate matter (PM2.5) air pollution outbreaks have recently occurred frequently in China. However, evidence of the associations between short-term exposure to PM2.5 and cardiovascular morbidity is still limited in China. This study aimed to evaluate the associations between PM2.5 and hospital emergency room visits (ERVs) for cardiovascular diseases in urban areas in Beijing. Daily counts of cardiovascular ERVs were collected from ten large general hospitals from Jan 1 to Dec 31, 2013. Air pollution data were obtained from the Beijing Environmental Protection Bureau including 17 monitoring stations...
September 30, 2016: Environmental Pollution
Tzu-Yu Shao, Ling-Hui Hsu, Chien-Hui Chien, Bor-Luen Chiang
Recent studies have revealed various Foxp3(-) regulatory T (Treg) cell subsets effectively protect mice from colitis. In the present study, we demonstrated that B cells induced a particular subset of regulatory T (Treg-of-B) cells, expressing programmed cell death 1 (PD-1), inducible costimulator (ICOS), lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), and OX-40, did not express Foxp3. Treg-of-B cells produced abundant levels of IL-10 and low levels of IL-4 and TGF-β...
2016: Scientific Reports
Didem Ozkazanc, Digdem Yoyen-Ermis, Ece Tavukcuoglu, Yahya Buyukasik, Gunes Esendagli
To cope with immune responses, tumor cells implement elaborate strategies such as adaptive resistance and induction of T cell exhaustion. T cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of costimulatory molecules to T cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukemia-derived costimulatory signals on CD4(+) helper T (Th) cell exhaustion which may limit anti-tumor immunity...
August 27, 2016: Immunology
Songping Wang, Pamela A G Clarke, Roderick Davis, Salma Mumuni, Bernard Kwabi-Addo
Sex steroid hormones have been reported to induce inflammation causing dysregulation of cytokines in prostate cancer cells. However, the underlying epigenetic mechanism has not well been studied. The objective of this study was to evaluate the effect of sex steroid hormones on epigenetic DNA methylation changes in prostate cancer cells using a signature PCR methylation array panel that correspond to 96 genes with biological function in the human inflammatory and autoimmune signals in prostate cancer. Of the 96-gene panel, 32 genes showed at least 10% differentially methylation level in response to hormonal treatment when compared to untreated cells...
October 2016: Cytokine
Tadashi Ashizawa, Akira Iizuka, Chizu Nonomura, Ryota Kondou, Chie Maeda, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Koji Maruyama, Ken Yamaguchi, Ikumi Katano, Mamoru Ito, Yasuto Akiyama
PURPOSE: Humanized mouse models using NOD/Shi-scid-IL2r gammanull (NOG) and NOD/LtSz-scid IL2r gamma null (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xeno-graft versus host disease (xeno-GVHD) in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility (MHC) class I and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the anti-tumor effect of anti-programmed death-1 (PD-1) antibody...
July 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Fangfang Huang, Yanxia Luo, Yuming Guo, Lixin Tao, Qin Xu, Chao Wang, Anxin Wang, Xia Li, Jin Guo, Aoshuang Yan, Xiuhua Guo
BACKGROUND: The impact of particulate matter (PM) on stroke may vary by particle size, stroke subtype, and patient characteristics and temperature. We examined the association of stroke admissions with PM in different subgroups in Beijing, China, during 2013-2014. METHODS AND RESULTS: A time-stratified case-crossover design was used to assess the relation between PM of different particle sizes and hospital admissions for ischemic and hemorrhagic stroke. Stratified analyses were performed by age, sex, and temperature...
July 2016: Journal of the American Heart Association
Shinkyo Yoon, Byung Woog Kang, Su Yeon Park, Hye Jin Kim, Jun Seok Park, Gyu Seog Choi, Jong Gwang Kim
PURPOSE: Genetic polymorphisms in genes involved in the immune response are already known to affect the anti-tumor immune response. This study systematically investigated the association of 14 functional SNPs in a panel of 7 genes (CCL2, CCR2, NT5E, IDO1, LAG3, PDL1, and PDCD1) involved in immune response checkpoints with the survival outcomes of Korean patients with colorectal cancer (CRC). METHODS: The genomic DNA from 668 patients with curatively resected CRC was analyzed using a Sequenom MassARRAY, along with the association with recurrence-free survival (RFS) and overall survival (OS)...
August 2016: Journal of Cancer Research and Clinical Oncology
Ewa Kozela, Ana Juknat, Fuying Gao, Nathali Kaushansky, Giovanni Coppola, Zvi Vogel
BACKGROUND: Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. METHODS: Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells...
2016: Journal of Neuroinflammation
Scott J Antonia, Johan F Vansteenkiste, Edmund Moon
Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1...
2016: American Society of Clinical Oncology Educational Book
Y Sunakawa, S Cao, N B Volz, M D Berger, D Yang, A Parekh, W Zhang, S Matsusaka, Y Ning, S Stremitzer, S Stintzing, A Sebio, S Okazaki, T Wakatsuki, M Azuma, M Watanabe, W Koizumi, A H Wu, H-J Lenz
Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set...
May 31, 2016: Pharmacogenomics Journal
Atsushi Kadowaki, Sachiko Miyake, Ryoko Saga, Asako Chiba, Hideki Mochizuki, Takashi Yamamura
The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of 'induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS)...
2016: Nature Communications
Randy F Sweis, Stefani Spranger, Riyue Bao, Gladell P Paner, Walter M Stadler, Gary Steinberg, Thomas F Gajewski
Muscle-invasive urothelial bladder cancer is a common malignancy with poor outcomes for which immune checkpoint blockade is now showing promise. Despite clinical activity of PD-1/PD-L1-targeted therapy in this disease, most patients do not benefit and resistance mechanisms remain unknown. The non-T-cell-inflamed tumor microenvironment correlates with poor prognosis and resistance to immunotherapies. In this study, we determined tumor-oncogenic pathways correlating with T-cell exclusion. We first establish in this report that T-cell-inflamed bladder tumors can be identified by immune gene expression profiling with concordance with CD8(+) T-cell infiltration...
July 2016: Cancer Immunology Research
G Nunnari, P Fagone, F Condorelli, F Nicoletti, L Malaguarnera, M Di Rosa
OBJECTIVES: T-cell repertoire dysfunction characterizes human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms remain unclear. Disease progression is probably due to a profound dysregulation of Th1, Th2, Th17 and Treg patterns. The aim of this study was to analyze the features of CD4+ T cells in HIV-positive patients with different viroimmunological profile. METHODS: we used a gene expression dataset of CD4+ T cells from healthy donors, HIV+ naive patients and Elite Controllers (EC), obtained from the NCBI Gene Expression Omnibus (GEO, http://www...
July 2016: Cytokine
Matthieu Collin
INTRODUCTION: Immune checkpoint inhibitors, like anti-PD-1/PD-L1 antibodies, are revolutionizing therapeutic concepts in the treatment of cancer. Said class of drugs will represent a multi-billion dollar market over the coming decade. Many companies have therefore developed important patent activities in the field. AREAS COVERED: The present review gives an overview of the patent literature during the period 2010-2015 in the field of immune checkpoint inhibitors...
May 2016: Expert Opinion on Therapeutic Patents
Amy M Jimenez, Junghee Lee, Jonathan K Wynn, Mark S Cohen, Stephen A Engel, David C Glahn, Keith H Nuechterlein, Eric A Reavis, Michael F Green
Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls...
2016: Frontiers in Psychology
John R Webb, Katy Milne, David R Kroeger, Brad H Nelson
OBJECTIVE: As a negative regulator of T cells, Programmed Death Ligand 1 (PD-L1) is both an indicator and inhibitor of anti-tumor immune responses, which has led to confusion about its prognostic significance. We investigated the primary source of PD-L1 expression in epithelial ovarian cancer and its relationship to tumor-infiltrating lymphocytes (TIL) and associated gene products. METHODS: Tissue microarrays containing high-grade serous carcinomas (HGSC) and endometrioid, clear cell and mucinous ovarian cancers from optimally debulked patients were assessed by immunohistochemistry for expression of PD-L1 and other markers (CD68, CD3, CD8, PD-1, CD103, FoxP3 and CD25)...
May 2016: Gynecologic Oncology
Szu-Ying Chen, Wan-Tseng Hsu, Yi-Lien Chen, Chien-Hui Chien, Bor-Luen Chiang
Rheumatoid arthritis (RA) is an autoimmune disease in which dysregulated immune cells primarily target synovial joints. Despite recent advances in the treatment of RA, including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug strategies, remission rates remain suboptimal. Previous studies have demonstrated that the adoptive transfer of induced regulatory T cells (iTregs) was effective in treating a murine model of collagen-induced arthritis (CIA). The objective of this study was to develop optimal potential iTreg-based therapy for CIA by adoptively transferring LAG3(+) Treg-of-B cells...
April 2016: Journal of Autoimmunity
Meghan E Turnis, Deepali V Sawant, Andrea L Szymczak-Workman, Lawrence P Andrews, Greg M Delgoffe, Hiroshi Yano, Amy J Beres, Peter Vogel, Creg J Workman, Dario A A Vignali
Regulatory T (Treg) cells pose a major barrier to effective anti-tumor immunity. Although Treg cell depletion enhances tumor rejection, the ensuing autoimmune sequelae limits its utility in the clinic and highlights the need for limiting Treg cell activity within the tumor microenvironment. Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function. Using an IL-35 reporter mouse, we observed substantial enrichment of IL-35(+) Treg cells in tumors. Neutralization with an IL-35-specific antibody or Treg cell-restricted deletion of IL-35 production limited tumor growth in multiple murine models of human cancer...
February 16, 2016: Immunity
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