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https://www.readbyqxmd.com/read/28710387/protein-tyrosine-phosphatase-inhibition-prevents-experimental-cerebral-malaria-by-precluding-cxcr3-expression-on-t-cells
#1
Kristin M Van Den Ham, Logan K Smith, Martin J Richer, Martin Olivier
Cerebral malaria induced by Plasmodium berghei ANKA infection is dependent on the sequestration of cytotoxic T cells within the brain and augmentation of the inflammatory response. Herein, we demonstrate that inhibition of protein tyrosine phosphatase (PTP) activity significantly attenuates T cell sequestration within the brain and prevents the development of neuropathology. Mechanistically, the initial upregulation of CXCR3 on splenic T cells upon T cell receptor stimulation was critically decreased through the reduction of T cell-intrinsic PTP activity...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705380/air-pollution-and-hospitalization-for-acute-myocardial-infarction-in-china
#2
Hui Liu, Yaohua Tian, Xiao Xiang, Kexin Sun, Juan Juan, Jing Song, Yaying Cao, Beibei Xu, Yonghua Hu
There is growing interest in the association between ambient air pollution and acute myocardial infarction (AMI). The objective of this study was to explore the association in 14 Chinese cities using a time-stratified case-crossover design. We identified 80,787 hospital admissions for AMI between January 1, 2014 and December 31, 2015 from electronic hospitalization summary reports. Conditional logistic regression was used to estimate the percent changes with 95% confidence intervals (CIs) in AMI admissions in relation to an interquartile range increase in ambient air pollutant concentrations...
June 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28689791/peanut-specific-tr1-cells-induced-in-vitro-from-allergic-individuals-are-functionally-impaired
#3
Laurence Pellerin, Jennifer Anne Jenks, Sharon Chinthrajah, Tina Dominguez, Whitney Block, Xiaoying Zhou, Arram Noshirvan, Silvia Gregori, Maria Grazia Roncarolo, Kari Christine Nadeau, Rosa Bacchetta
BACKGROUND: Peanut allergy is a life threatening condition which lacks regulatory-approved treatment. T regulatory type 1 (Tr1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro using tolerogenic dendritic cells (DC-10). Whether or not oral immunotherapy (OIT) leads to antigen-specific Tr1 cell induction has not been established. OBJECTIVES: To determine whether peanut-specific Tr1 cells can be generated in vitro from peripheral blood of peanut allergic (PA) individuals at baseline or during OIT, and whether they are functional as compared to peanut-specific Tr1 cells induced from healthy controls (HC)...
July 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28682499/high-dose-dexamethasone-or-all-trans-retinoic-acid-restores-the-balance-of-macrophage-toward-m2-in-immune-thrombocytopenia
#4
Q Feng, M Xu, Y Y Yu, Y Hou, X Mi, Y X Sun, S Ma, X Y Zuo, L L Shao, M Hou, X H Zhang, J Peng
Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune-tolerance in antigen-presenting cells (APCs) and cross-communication between APCs and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and possess diverse immunological functions OBJECTIVES: To investigate the imbalance of M1/M2 in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans retinoic acid (ATRA) could restore this imbalance METHODS: Numbers of M1 and M2 in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence...
July 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#5
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28633489/effects-of-early-pregnancy-on-uterine-lymphocytes-and-endometrial-expression-of-immune-regulatory-molecules-in-dairy-heifers1
#6
Sreelakshmi Vasudevan, Manasi M Kamat, Sadhat S Walusimbi, Joy L Pate, Troy L Ott
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested...
June 19, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#7
REVIEW
Maria G Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the PD1/PDL1 and CTLA4 pathways has led to significant clinical benefit either as monotherapy or in combination therapy. Moreover, checkpoint receptors such as LAG3, TIM3 and KIRs are also being investigated as potential immunotherapeutic targets...
June 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28554030/ambient-sulfur-dioxide-levels-associated-with-reduced-risk-of-initial-outpatient-visits-for-tuberculosis-a-population-based-time-series-analysis
#8
Erjia Ge, Min Fan, Hong Qiu, Howard Hu, Linwei Tian, Xiaomeng Wang, Guozhang Xu, Xiaolin Wei
BACKGROUND: Recent biochemical studies suggest that exogenous sulfur dioxide (SO2) at low concentrations may have been beneficial in inhibiting mycobacteria tuberculosis (TB) growth. However, there is a dearth of population-based studies. OBJECTIVES: To examine the association of ambient SO2 levels and initial TB outpatient visits. METHODS: In Ningbo, China, we collected all daily initial outpatient visits for TB and routinely air pollution monitoring data between January 2009 and December 2013...
May 26, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28551033/the-molecular-signature-of-murine-t-cell-homeostatic-proliferation-reveals-both-inflammatory-and-immune-inhibition-patterns
#9
Karen A Fortner, Jeffrey P Bond, James W Austin, Jeremy M Boss, Ralph C Budd
T lymphocyte homeostatic proliferation, driven by the engagement of T cell antigen receptor with self-peptide/major histocompatibility complexes, and signaling through the common γ-chain-containing cytokine receptors, is critical for the maintenance of the T cell compartment and is regulated by the Fas death receptor (Fas, CD95). In the absence of Fas, Fas-deficient lymphoproliferation spontaneous mutation (lpr) mice accumulate homeostatically expanded T cells. The functional consequences of sequential rounds of homeostatic expansion are not well defined...
May 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#10
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#11
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511719/interleukin-10-producing-lag3-regulatory-t-cells-are-associated-with-disease-activity-and-abatacept-treatment-in-rheumatoid-arthritis
#12
Shinichiro Nakachi, Shuji Sumitomo, Yumi Tsuchida, Haruka Tsuchiya, Masanori Kono, Rika Kato, Keiichi Sakurai, Norio Hanata, Yasuo Nagafuchi, Shoko Tateishi, Hiroko Kanda, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4(+)CD25(-)LAG3(+) T cells (LAG3(+) Tregs) and their association with rheumatoid arthritis (RA). METHODS: LAG3(+) Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects...
May 16, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#13
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28416578/withdrawn-quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#14
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28344863/tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#15
Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#16
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325534/association-between-meteorological-factors-and-hepatitis-a-in-spain-2010-2014
#17
Pedro Gullón, Carmen Varela, Elena Vanessa Martínez, Diana Gómez-Barroso
BACKGROUND: There is growing concern of how climate change could affect public health, due to the increase number of extreme climate events. Hence, the study of the role that climate events play on the distribution of waterborne diseases, like Hepatitis A, could be key for developing new prevention approaches. OBJECTIVE: To investigate the association between climate factors and Hepatitis A in Spain between 2010 and 2014. METHODS: Weekly Hepatitis A cases between 2010 and 2014 were obtained from the Spanish Epidemiology Surveillance Network...
March 18, 2017: Environment International
https://www.readbyqxmd.com/read/28277274/therapeutic-reversal-of-food-allergen-sensitivity-by-mature-retinoic-acid-differentiated-dendritic-cell-induction-of-lag3-cd49b-foxp3-regulatory-t%C3%A2-cells
#18
Wojciech Dawicki, Chunyan Li, Jennifer Town, Xiaobei Zhang, John R Gordon
BACKGROUND: Anaphylaxis is a life-threatening condition for which we have limited therapeutic options. Although specific immunotherapy for food allergies is becoming more effective, it is still laborious and carries substantial risk of adverse events. On the other hand, regulatory dendritic cell (DC) therapy is effective in mouse models of allergic disease and has been shown to work with TH2 cells from atopic asthmatic patients. OBJECTIVE: We assessed whether DC immunotherapy could reverse food allergen sensitivity in mouse models to provide proof of concept relating to their use in the clinic...
May 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28270499/pd-l1-is-a-therapeutic-target-of-the-bromodomain-inhibitor-jq1-and-combined-with-hla-class-i-a-promising-prognostic-biomarker-in-neuroblastoma
#19
Ombretta Melaiu, Marco Mina, Marco Chierici, Renata Boldrini, Giuseppe Jurman, Paolo Romania, Valerio D'Alicandro, Maria Chiara Benedetti, Aurora Castellano, Tao Liu, Cesare Furlanello, Franco Locatelli, Doriana Fruci
PURPOSE: This study sought to evaluate expression of PD-L1 and HLA class I on neuroblastoma cells and PD-1 and LAG3 on tumor-infiltrating lymphocytes to better define patient risk-stratification and understand whether this tumor may benefit from therapies targeting immune-checkpoint molecules. EXPERIMENTAL DESIGN: In situ immunohistochemical staining for PD-L1, HLA class I, PD-1 and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T cell-density, and correlated with clinical outcome...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28258692/lag3-cd223-as-a-cancer-immunotherapy-target
#20
REVIEW
Lawrence P Andrews, Ariel E Marciscano, Charles G Drake, Dario A A Vignali
Despite the impressive impact of CTLA4 and PD1-PDL1-targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene-3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity...
March 2017: Immunological Reviews
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