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https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#1
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#2
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27835902/squamous-cell-carcinomas-escape-immune-surveillance-via-inducing-chronic-activation-and-exhaustion-of-cd8-t-cells-co-expressing-pd-1-and-lag-3-inhibitory-receptors
#3
Ameet K Mishra, Tanya Kadoishi, Xiaoguang Wang, Emily Driver, Zhangguo Chen, Xiao-Jing Wang, Jing H Wang
Squamous cell carcinoma (SCC) is the second commonest type of skin cancer. Moreover, about 90% of head and neck cancers are SCCs. SCCs develop at a significantly higher rate under chronic immunosuppressive conditions, implicating a role of immune surveillance in controlling SCCs. It remains largely unknown how SCCs evade immune recognition. Here, we established a mouse model by injecting tumor cells derived from primary SCCs harboring KrasG12D mutation and Smad4 deletion into wild-type (wt) or CD8-/- recipients...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784399/-immune-tolerance-mediated-by-tim-3-lag-3-and-btla-and-their-reversion-in-hematological-malignancies-review
#4
Shao-Hua Chen, Xiang-Feng Zha, Yang-Qiu Li
The main mechanism of tumor immune suppression is due to the T cell exhaustion which is mediated by abnormal expression of T-cell immunosuppressive receptors in immune cells. Blocking these molecules may restore partial or all functions of T cells. This article reviews the advance on the role of the newly discovered T cell immuno-suppressive receptors such as TIM-3, LAG-3 and BTLA, including their mediated T cell-immune tolerance and the study of targeted immunotherapy in hematological malignancies, so as to provide the new strategy for immune-targeted therapy for hematological malignancies...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27782175/angiotensin-ii-type-1-receptor-at1r-regulates-expansion-differentiation-and-functional-capacity-of-antigen-specific-cd8-t-cells
#5
João Luiz Silva-Filho, Celso Caruso-Neves, Ana Acacia Sá Pinheiro
Angiotensin II (Ang II) and its receptor AT1 (AT1R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT1R effects using pharmacological tools, which do not target only Ang II/AT1R axis. The specific role of AT1R expressed by antigen-specific CD8(+) T cells is unknown. Then we immunized transgenic mice expressing a T-cell receptor specific for SIINFEKL epitope (OT-I mice) with sporozoites of the rodent malaria parasite Plasmodium berghei expressing the cytotoxic epitope SIINFEKL...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725355/immune-exhaustion-during-chronic-infections-in-cattle
#6
Satoru Konnai, Shiro Murata, Kazuhiko Ohashi
Recently, dysfunction of antigen-specific T cells is well documented as T-cell exhaustion and has been defined by the loss of effector functions during chronic infections and cancer in human. The exhausted T cells are characterized phenotypically by the surface expression of immunoinhibitory receptors, such as programmed death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and cytotoxic T-lymphocyte antigen 4 (CTLA-4). However, there is still a fundamental lack of knowledge about the immunoinhibitory receptors in the fields of veterinary medicine...
October 8, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27709311/transmission-dynamics-of-the-west-nile-virus-in-mosquito-vector-populations-under-the-influence-of-weather-factors-in-the-danube-delta-romania
#7
Ani Ioana Cotar, Elena Falcuta, Liviu Florian Prioteasa, Sorin Dinu, Cornelia Svetlana Ceianu, Shlomit Paz
Mosquitoes were collected in the Danube Delta during the active seasons of 2011-2013. For Culex spp. mosquitoes, the abundance was calculated. Culex pipiens (sensu lato), (s.l.) and Culex modestus pools were tested for the presence of West Nile virus (WNV) genome, and the maximum likelihood of the infection rate was established. Mean daily temperatures and precipitation were obtained for the closest meteorological station. A negative binominal model was used to evaluate linkages between the temperature/precipitation and mosquito population size...
October 5, 2016: EcoHealth
https://www.readbyqxmd.com/read/27708227/t-cell-responses-against-cd19-pediatric-acute-lymphoblastic-leukemia-mediated-by-bispecific-t-cell-engager-bite-are-regulated-contrarily-by-pd-l1-and-cd80-cd86-on-leukemic-blasts
#8
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27704876/cd4-foxp3-il-10-tr1-cells-promote-relapse-of-diffuse-large-b-cell-lymphoma-by-enhancing-the-survival-of-malignant-b-cells-and-suppressing-antitumor-t-cell-immunity
#9
Guozhen Liu, Jing Luan, Qiang Li
Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy. Complete remission can be achieved in most patients by conventional treatment with rituximab and chemotherapy. However, a subset of remission individuals will develop a relapsed disease for obscure reasons. CD4(+)Foxp3(-)IL-10(+) cell (Tr1) is a novel cell subtype with the capacity to suppress pro-inflammatory responses, but has not been extensively studied in most tumors. In this study, we investigated the potential role of Tr1 cells in DLBCL...
October 5, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27683580/tr1-like-t-cells-an-enigmatic-regulatory-t-cell-lineage
#10
Anna Malgorzata White, David C Wraith
The immune system evolved to respond to foreign invaders and prevent autoimmunity to self-antigens. Several types of regulatory T cells facilitate the latter process. These include a subset of Foxp3(-) CD4(+) T cells able to secrete IL-10 in an antigen-specific manner, type 1 regulatory (Tr1) T cells. Although their suppressive function has been confirmed both in vitro and in vivo, their phenotype remains poorly defined. It has been suggested that the surface markers LAG-3 and CD49b are biomarkers for murine and human Tr1 cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27641216/agonistic-anti-cd40-therapy-synergizes-with-lag-3-blocking-antibodies%C3%A2
#11
Philipp Müller, Daniela S Thommen, Alfred Zippelius
No abstract text is available yet for this article.
September 19, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27630165/long-lived-cd4-ifn-%C3%AE-t-cells-rather-than-short-lived-cd4-ifn-%C3%AE-il-10-t-cells-initiate-rapid-il-10-production-to-suppress-anamnestic-t-cell-responses-during-secondary-malaria-infection
#12
Ana Villegas-Mendez, Colette A Inkson, Tovah N Shaw, Patrick Strangward, Kevin N Couper
CD4(+) T cells that produce IFN-γ are the source of host-protective IL-10 during primary infection with a number of different pathogens, including Plasmodium spp. The fate of these CD4(+)IFN-γ(+)IL-10(+) T cells following clearance of primary infection and their subsequent influence on the course of repeated infections is, however, presently unknown. In this study, utilizing IFN-γ-yellow fluorescent protein (YFP) and IL-10-GFP dual reporter mice, we show that primary malaria infection-induced CD4(+)YFP(+)GFP(+) T cells have limited memory potential, do not stably express IL-10, and are disproportionately lost from the Ag-experienced CD4(+) T cell memory population during the maintenance phase postinfection...
September 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27605882/specific-cd8-t-cell-response-immunotherapy-for-hepatocellular-carcinoma-and-viral-hepatitis
#13
REVIEW
Elia Moreno-Cubero, Juan-Ramón Larrubia
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment...
July 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27539525/-the-impact-of-ambient-fine-particulate-matter-on-the-blood-pressure-of-an-urban-population-in-shanghai-china-a-panel-study
#14
W X Xu, R J Chen, H D Kan
OBJECTIVE: To investigate the impact of particulate matter 2.5 (PM2.5) on the blood pressure of urban residents in Shanghai, China. METHODS: A panel study was conducted from May 27(th) to June 5(th) 2014 in a cohort of 30 adults in an urban community. Participants were 50-80 years old, had lived in the community for at least 5 years, and had a good health status. Key exclusion criteria were current smoking, smoking during the last 3 years, passive smoking, alcohol consumption, and severe cardiopulmonary disease...
August 6, 2016: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/27533257/effects-of-air-pollutant-exposure-on-acute-myocardial-infarction-according-to-gender
#15
Tássia Soldi Tuan, Taís Siqueira Venâncio, Luiz Fernando Costa Nascimento
Background: There is evidence of the effects of air pollution on hospital admissions due to cardiovascular diseases, including myocardial infarction. Objective: To estimate the association between exposure to air pollutants and hospital admissions due to myocardial infarction according to gender, between January 1st 2012 and December 31st 2013, in São Jose dos Campos-SP. Methods: An ecological time series study was carried out with daily data of admissions due to AMI, pollutants CO, O3, PM10, SO2, and NO2, according to gender...
September 2016: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/27533016/t-cell-factor-1-expressing-memory-like-cd8-t-cells-sustain-the-immune-response-to-chronic-viral-infections
#16
Daniel T Utzschneider, Mélanie Charmoy, Vijaykumar Chennupati, Laurène Pousse, Daniela Pais Ferreira, Sandra Calderon-Copete, Maxime Danilo, Francesca Alfei, Maike Hofmann, Dominik Wieland, Sylvain Pradervand, Robert Thimme, Dietmar Zehn, Werner Held
Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature...
August 16, 2016: Immunity
https://www.readbyqxmd.com/read/27477778/il-2-in-the-tumor-microenvironment-is-necessary-for-wiskott-aldrich-syndrome-protein-deficient-nk-cells-to-respond-to-tumors-in-vivo
#17
Joanna S Kritikou, Carin I M Dahlberg, Marisa A P Baptista, Arnika K Wagner, Pinaki P Banerjee, Lavesh Amar Gwalani, Cecilia Poli, Sudeepta K Panda, Klas Kärre, Susan M Kaech, Fredrik Wermeling, John Andersson, Jordan S Orange, Hanna Brauner, Lisa S Westerberg
To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFNγ upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27470968/pd-1-pd-l1-blockade-enhances-t-cell-activity-and-antitumor-efficacy-of-imatinib-in-gastrointestinal-stromal-tumors
#18
Adrian M Seifert, Shan Zeng, Jennifer Q Zhang, Teresa S Kim, Noah A Cohen, Michael J Beckman, Benjamin D Medina, Joanna H Maltbaek, Jennifer K Loo, Megan H Crawley, Ferdinand Rossi, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
PURPOSE: Tyrosine kinase inhibitors are effective in gastrointestinal stromal tumor (GIST), but often are of transient benefit as resistance commonly develops. Immunotherapy, particularly blockade of the inhibitory receptor programmed death 1 (PD-1) or the ligand programmed death ligand 1 (PD-L1), has shown effectiveness in a variety of cancers. The functional effects of PD-1/PD-L1 blockade are unknown in GIST. EXPERIMENTAL DESIGN: We analyzed tumor and matched blood samples from 85 patients with GIST and determined the expression of immune checkpoint molecules using flow cytometry...
July 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27467927/polyfunctional-melan-a-specific-tumor-reactive-cd8-t-cells-elicited-by-dacarbazine-treatment-before-peptide-vaccination-depends-on-akt-activation-sustained-by-icos
#19
Ornella Franzese, Belinda Palermo, Cosmo Di Donna, Isabella Sperduti, Virginia Ferraresi, Helena Stabile, Angela Gismondi, Angela Santoni, Paola Nisticò
The identification of activation pathways linked to antitumor T-cell polyfunctionality in long surviving patients is of great relevance in the new era of immunotherapy. We have recently reported that dacarbazine (DTIC) injected one day before peptide-vaccination plus IFN-α improves the antitumor lytic activity and enlarges the repertoire of Melan-A-specific T-cell clones, as compared with vaccination alone, impacting the overall survival of melanoma patients. To identify the mechanisms responsible for this improvement of the immune response, we have analyzed the endogenous and treatment-induced antigen (Ag)-specific response in a panel of Melan-A-specific CD8(+) T-cell clones in terms of differentiation phenotype, inhibitory receptor profile, polyfunctionality and AKT activation...
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27430272/cooperation-of-pd-1-and-lag-3-contributes-to-t-cell-exhaustion-in-anaplasma-marginale-infected-cattle
#20
Tomohiro Okagawa, Satoru Konnai, James R Deringer, Massaro W Ueti, Glen A Scoles, Shiro Murata, Kazuhiko Ohashi, Wendy C Brown
The CD4(+) T-cell response is central for the control of Anaplasma marginale infection in cattle. However, the infection induces a functional exhaustion of antigen-specific CD4(+) T cells in cattle immunized with A. marginale outer membrane proteins or purified outer membranes (OMs), which presumably facilitates the persistence of this rickettsia. In the present study, we hypothesize that T-cell exhaustion following infection is induced by the upregulation of immunoinhibitory receptors on T cells, such as programmed death 1 (PD-1) and lymphocyte activation gene 3 (LAG-3)...
October 2016: Infection and Immunity
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