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https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#1
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#3
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28894272/t-cell-tolerance-and-exhaustion-in-the-clearance-of-echinococcus-multilocularis-role-of-inoculum-size-in-a-quantitative-hepatic-experimental-model
#4
Chuanshan Zhang, Yingmei Shao, Shuting Yang, Xiaojuan Bi, Liang Li, Hui Wang, Ning Yang, Zhide Li, Cheng Sun, Liang Li, Guodong Lü, Tuerganaili Aji, Dominique A Vuitton, Renyong Lin, Hao Wen
The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890294/analysis-of-non-small-cell-lung-cancer-microenvironment-indicates-preponderance-of-t-cell-exhaustion-marker-expression
#5
Hui Zhou, Tingwei Liu, Zanfeng Wang
Lung cancer metastasis causes 70% of an estimated 1.4 million deaths per annum. The major shortcoming in lung cancer is the tendency to have inherent or develop acquired resistance to chemotherapy. It is now evolving that such resistance might develop due to differential contribution and interaction with tumor microenvironment, stromal cells, and the extracellular matrix. The objective of the current study was to define the lung cancer tumor microenvironment. We have identified multiple tumor-infiltrating T lymphocyte subsets in patients with lung cancer, which were independent of disease stage...
September 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28833046/ahr-activation-increases-il-2-production-by-alloresponding-cd4-t-cells-initiating-the-differentiation-of-mucosal-homing-tim3-lag3-tr1-cells
#6
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3(+) Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4(+) T cells that accompany the differentiation of AhR-Tr1 cells during the CD4(+) T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
August 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28814904/the-journey-of-rheumatoid-arthritis-patients-a-review-of-reported-lag-times-from-the-onset-of-symptoms
#7
REVIEW
Alaa S Barhamain, Rami F Magliah, Mohammad H Shaheen, Shurooq F Munassar, Ayman M Falemban, Mohammed M Alshareef, Hani M Almoallim
BACKGROUND: Even after achieving tremendous advances in diagnosis and treatment of rheumatoid arthritis (RA), many of the patients undergo delays in diagnosis and initiation of treatment, which leads to worsening of the condition and poor prognosis. OBJECTIVE: The objective of this study was to perform a literature review to quantify the lag times in diagnosis and treatment of RA and study the reported factors associated with it. METHODS: The authors searched literature published until September 2016 in electronic full-text and abstract databases and hand-searched the suitable articles...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#8
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28783703/lag3-limits-regulatory-t-cell-proliferation-and-function-in-autoimmune-diabetes
#9
Qianxia Zhang, Maria Chikina, Andrea L Szymczak-Workman, William Horne, Jay K Kolls, Kate M Vignali, Daniel Normolle, Maria Bettini, Creg J Workman, Dario A A Vignali
Inhibitory receptors (IRs) are pivotal in controlling T cell homeostasis because of their intrinsic regulation of conventional effector T (Tconv) cell proliferation, viability, and function. However, the role of IRs on regulatory T cells (Tregs) remains obscure because they could be required for suppressive activity and/or limit Treg function. We evaluated the role of lymphocyte activation gene 3 (LAG3; CD223) on Tregs by generating mice in which LAG3 is absent on the cell surface of Tregs in a murine model of type 1 diabetes...
March 31, 2017: Science Immunology
https://www.readbyqxmd.com/read/28766553/regulatory-t-cells-with-superior-immunosuppressive-capacity-emigrate-from-the-inflamed-colon-to-draining-lymph-nodes
#10
Y Nakanishi, R Ikebuchi, T Chtanova, Y Kusumoto, H Okuyama, T Moriya, T Honda, K Kabashima, T Watanabe, Y Sakai, M Tomura
Foxp3(+) Regulatory T cells (Tregs) play a critical role in the maintenance of colon homeostasis. Here we utilized photoconvertible KikGR mice to track immune cells from the caecum and ascending (proximal) colon in the steady state and DSS-induced colitis. We found that Tregs from the proximal colon (colonic migratory Tregs) migrated exclusively to the distal part of mesenteric lymph nodes (dMLN) in an S1PR1-dependent process. In the steady state, colonic migratory CD25(+) Tregs expressed higher levels of CD103, ICOS, LAG3 and CTLA-4 in comparison with pre-existing LN Tregs...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28710387/protein-tyrosine-phosphatase-inhibition-prevents-experimental-cerebral-malaria-by-precluding-cxcr3-expression-on-t-cells
#11
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
#12
MULTICENTER STUDY
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...
September 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28689791/peanut-specific-tr1-cells-induced-in-vitro-from-allergic-individuals-are-functionally-impaired
#13
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-macrophages-towards-m2-in-immune-thrombocytopenia
#14
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
Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients. SUMMARY: Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP...
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
#15
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-heifers
#16
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...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#17
REVIEW
Maria Giovanna 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 programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy...
August 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
#18
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...
September 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
#19
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...
August 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
#20
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
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