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https://www.readbyqxmd.com/read/28492391/hepatitis-c-virus-drives-increased-type-i-interferon-associated-impairments-associated-with-fibrosis-severity-in-antiretroviral-treatment-treated-hiv-1-hepatitis-c-virus-coinfected-individuals
#1
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28482851/checkpoint-inhibitors-in-hematological-malignancies
#2
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28468072/-impact-of-daily-mean-temperature-cold-spells-and-heat-waves-on-stroke-mortality-a-multivariable-meta-analysis-from-12-counties-of-hubei-province-china
#3
Y Q Zhang, C H Yu, J Z Bao
Objective: To assess the acute effects of daily mean temperature, cold spells, and heat waves on stroke mortality in 12 counties across Hubei province, China. Methods: Data related to daily mortality from stroke and meteorology in 12 counties across Hubei province during 2009-2012, were gathered. Distributed lag nonlinear model (DLNM) was first used, to estimate the county-specific associations between daily mean temperature, cold spells, heat waves and stroke mortality. Multivariate Meta-analysis was then applied to pool the community-specific relationships between temperature and stroke mortality (exposure-response relationship) as well as both cold- and- heat-associated risks on mortality at different lag days (lag-response relationship)...
April 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28466380/differences-of-temporal-dynamics-and-signal-complexity-of-gamma-band-oscillations-in-first-episode-psychosis-during-a-working-memory-task
#4
Pascal Missonnier, Logos Curtis, Joseph Ventura, François R Herrmann, Marco C G Merlo
Gamma band oscillations participate in the temporal binding needed to synchronize cortical networks, involved in early sensory and short term memory processes. In earlier studies, alterations of these neurophysiological parameters have been found in psychotic disorders. To date no study has explored the temporal dynamics and signal complexity of gamma band oscillations in first episode psychosis (FEP). To address this issue, gamma band analysis was performed in 15 FEP patients and 18 healthy controls who successfully performed an adapted 2-back working memory task...
May 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28454880/expression-of-negative-immune-regulatory-molecules-pro-inflammatory-chemokine-and-cytokines-in-immunopathology-of-ecm-developing-mice
#5
Ashwin V Khandare, Deepali Bobade, Mangesh Deval, Tushar Patil, Bhaskar Saha, D Prakash
The pathological events in human cerebral malaria are mimicked in the experimental cerebral malaria (ECM) in Plasmodium berghei ANKA (PBA)-infected C57BL/6 mice. Although previously implied in ECM, the kinetics of cytokines and chemokines expression-an essential functional feature for defining causality in ECM development-remained untested. Herein, we characterized the immunopathological changes and the expression of negative immune regulatory molecules, cytokines and chemokines through asymptomatic (3days after infection, 3dpi), symptomatic (5dpi) and ECM (7dpi) stages in PBA-infected C57BL/6 mice...
April 25, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28434981/protein-transport-inhibitors-downregulate-the-expression-of-lag-3-on-regulatory-t-cells
#6
Sara Anvari, Andrea Grimbergen, Carla M Davis, George Makedonas
Modern immunologic studies demand increasing complexity because of a need to improve our understanding of the relationship between a cell's phenotype and its function. Regulatory T cells have been defined by a narrow set of phenotypic markers, however their actual functional capacity has not been determined at the single-cell level. Although the lymphocyte activation gene 3 (LAG-3; CD223) is a key marker for the identification of exhausted T cells, it may be useful also in resolving Treg subpopulations by indicating distinct functional breadths...
April 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#7
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28378637/primary-tr1-cells-from-metastatic-melanoma-eliminate-tumor-promoting-macrophages-through-granzyme-b-and-perforin-dependent-mechanisms
#8
Hongxia Yan, Ping Zhang, Xue Kong, Xianglian Hou, Li Zhao, Tianhang Li, Xiaozhou Yuan, Hongjun Fu
In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28356069/broad-induction-of-immunoregulatory-mechanisms-after-a-short-course-of-anti-il-7r%C3%AE-antibodies-in-nod-mice
#9
Cristina Vazquez-Mateo, Justin Collins, Michelle Fleury, Hans Dooms
BACKGROUND: Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of the insulin-producing β-cells in the pancreas. Therefore, approaches that effectively halt the pathogenic T cell response are predicted to have preventive or therapeutic benefit for type 1 diabetes patients. We previously demonstrated that long-term blocking of IL-7 signaling, which is critical for the survival and function of T cells, prevented and reversed type 1 diabetes in non-obese diabetic mice...
March 29, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28342386/association-between-environmental-factors-and-emergency-hospital-admissions-due-to-alzheimer-s-disease-in-madrid
#10
D R Culqui, C Linares, C Ortiz, R Carmona, J Díaz
INTRODUCTION: There are scarce studies of time series that analysed the short-term association between emergency hospital admissions due to Alzheimer's disease (AD) and environmental factors. The objective is to analyse the effect of heat waves, noise and air pollutants on urgent hospital admissions due to AD in Madrid. METHODS: Longitudinal ecological time series study was performed. The dependent variable was the emergency AD hospital admissions occurred in Madrid during the period 2001-2009...
March 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#11
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#12
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#13
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28320933/activin-a-co-opts-irf4-and-ahr-signaling-to-induce-human-regulatory-t-cells-that-restrain-asthmatic-responses
#14
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Aikaterini I Trochoutsou, Tess M Brodie, Nikolaos Poulos, Konstantinos Samitas, Maria Kapasa, Dimitris Konstantopoulos, Giannis Paraskevopoulos, Mina Gaga, Catherine M Hawrylowicz, Federica Sallusto, Georgina Xanthou
Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4(+) T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#15
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28277722/leader-team-complementarity-exploring-the-interactive-effects-of-leader-personality-traits-and-team-power-distance-values-on-team-processes-and-performance
#16
Jia Hu, Timothy A Judge
Integrating the leader trait perspective with dominance complementarity theory, we propose team power distance as an important boundary condition for the indirect impact of leader extraversion, agreeableness, and conscientiousness on team performance through a team's potency beliefs and through relational identification with the leader. Using time-lagged, 3-source data from 71 teams, we found that leader extraversion had a positive indirect impact on team in-role and extrarole performance through relational identification, but only for high power distance teams; leader conscientiousness had a positive influence on team in-role performance through team potency, but only for high power distance teams; and leader agreeableness had a positive effect on team in-role and extrarole performance via relational identification and on team in-role performance via team potency, but only for low power distance teams...
March 9, 2017: Journal of Applied Psychology
https://www.readbyqxmd.com/read/28224733/nk1-1-cd4-nkg2d-t-cells-suppress-dss-induced-colitis-in-mice-through-production-of-tgf-%C3%AE
#17
Xingxing Qian, Chunxia Hu, Sen Han, Zhijie Lin, Weiming Xiao, Yanbing Ding, Yu Zhang, Li Qian, Xiaoqing Jia, Guoqiang Zhu, Weijuan Gong
CD4(+) NKG2D(+) T cells are associated with tumour, infection and autoimmune diseases. Some CD4(+) NKG2D(+) T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4(+) NKG2D(+) T cells were further classified into NK1.1(-) CD4(+) NKG2D(+) and NK1.1(+) CD4(+) NKG2D(+) subpopulations. The frequency of NK1.1(-) CD4(+) NKG2D(+) cells decreased in inflamed colons, whereas more NK1.1(+) CD4(+) NKG2D(+) cells infiltrated into colons of mice with DSS-induced colitis...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#18
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28197385/prognostic-and-predictive-aspects-of-the-tumor-immune-microenvironment-and-immune-checkpoints-in-malignant-pleural-mesothelioma
#19
Elly Marcq, Vasiliki Siozopoulou, Jorrit De Waele, Jonas van Audenaerde, Karen Zwaenepoel, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#20
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
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