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https://www.readbyqxmd.com/read/28344869/il-15-tim-3-and-nk-cells-subsets-predict-responsiveness-to-anti-ctla-4-treatment-in-melanoma-patients
#1
Rossana Tallerico, Costanza M Cristiani, Elina Staaf, Cinzia Garofalo, Rosa Sottile, Mariaelena Capone, Yago Pico de Coaña, Gabriele Madonna, Eleonora Palella, Maria Wolodarski, Valentina Carannante, Domenico Mallardo, Ester Simeone, Antonio M Grimaldi, Sofia Johansson, Paolo Frumento, Elio Gulletta, Andrea Anichini, Francesco Colucci, Gennaro Ciliberto, Rolf Kiessling, Klas Kärre, Paolo A Ascierto, Ennio Carbone
Despite the success of immune checkpoint blockade in melanoma, the majority of patients do not respond. We hypothesized that the T and NK cell subset frequencies and expression levels of their receptors may predict responses and clinical outcome of anti-CTLA-4 treatment. We thus characterized the NK and T cell phenotype, as well as serum levels of several cytokines in 67 melanoma patients recruited in Italy and Sweden, using samples drawn prior to and during treatment. Survival correlated with low expression of the inhibitory receptor TIM-3 on circulating T and NK cells prior to and during treatment and with the increased frequency of mature circulating NK cells (defined as CD3(-)CD56(dim) CD16(+)) during treatment...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344866/cd13-hi-neutrophil-like-myeloid-derived-suppressor-cells-exert-immune-suppression-through-arginase-1-expression-in-pancreatic-ductal-adenocarcinoma
#2
Jing Zhang, Xiongfei Xu, Min Shi, Ying Chen, Danghui Yu, Chenyan Zhao, Yan Gu, Biao Yang, Shiwei Guo, Guiling Ding, Gang Jin, Chin-Lee Wu, Minghua Zhu
Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344199/association-of-toll-like-receptor-4-on-human-monocyte-subsets-and-vulnerability-characteristics-of-coronary-plaque-as-assessed-by-64-slice-multidetector-computed-tomography
#3
Yuichi Ozaki, Toshio Imanishi, Seiki Hosokawa, Tsuyoshi Nishiguchi, Akira Taruya, Takashi Tanimoto, Akio Kuroi, Takashi Yamano, Yoshiki Matsuo, Yasushi Ino, Hironori Kitabata, Takashi Kubo, Atsushi Tanaka, Takashi Akasaka
BACKGROUND: Although Toll-like receptor 4 (TLR-4) is involved in monocyte activation in patients with accelerated forms of atherosclerosis, the relationship between the expression of TLR-4 on circulating monocytes and coronary plaque vulnerability has not previously been evaluated. We investigated this relationship using 64-slice multidetector computed tomography (MDCT) in patients with stable angina pectoris (SAP).Methods and Results:We enrolled 65 patients with SAP who underwent MDCT...
March 24, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28341671/lipopolysaccharide-elicited-tslpr-expression-enriches-a-functionally-discrete-subset-of-human-cd14-cd1c-monocytes
#4
Francesco Borriello, Raffaella Iannone, Sarah Di Somma, Viviana Vastolo, Giuseppe Petrosino, Feliciano Visconte, Maddalena Raia, Giulia Scalia, Stefania Loffredo, Gilda Varricchi, Maria Rosaria Galdiero, Francescopaolo Granata, Luigi Del Vecchio, Giuseppe Portella, Gianni Marone
Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14(+) monocyte CCL17 production in response to LPS and IL-4...
March 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28335588/recovery-of-nk-cd56-cd3-cells-after-1-year-of-tenofovir-therapy-for-chronic-hepatitis-b-infection
#5
Hwan Hee Lee, Hyojeung Kang, Hyosun Cho
Natural killer (NK) cells have been reported to be dysfunctional in chronic hepatitis B (CHB) infection. However, the functional recovery of NK cells was not clearly understood under anti-viral therapeutic agents in CHB. In this study, we investigated the phenotypic changes of NK(CD56+CD3-) cells in terms of their functional markers (CD16, NKG2A, NKG2D) during tenofovir therapy in CHB. The frequency of NK(CD56+CD3-) cells in CHB patients was significantly increased after 12 months of tenofovir therapy when compared to baseline...
March 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28332287/pretransplant-numbers-of-cd16-monocytes-as-a-novel-biomarker-to-predict-acute-rejection-after-kidney-transplantation-a-pilot-study
#6
Thierry P P van den Bosch, Luuk B Hilbrands, Rens Kraaijeveld, Nicolle H R Litjens, Farhad Rezaee, Daan Nieboer, Ewout W Steyerberg, Judith A van Gestel, Dave L Roelen, Marian C Clahsen-van Groningen, Carla C Baan, Ajda T Rowshani
Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte-macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pre-transplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 no-rejections and 46 biopsy-proven rejections), and 33 healthy individuals...
March 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28332085/low-level-arsenic-causes-chronic-inflammation-and-suppresses-expression-of-phagocytic-receptors
#7
Priyanka Prasad, Dona Sinha
The impact of chronic low-level groundwater arsenic (As) exposure [in the range above the WHO-recommended limit of 10 g/L but ≤50 μg/L (permissible limit of As for many Asian countries)] was investigated for cross talk of inflammatory changes and expression of phagocytic receptors of exposed rural women (N, 45) from districts of 24 Parganas (south) and in matched control groups (N, 43) [As ≤10 μg/L] from the same district. Systemic inflammation was evident from the upregulated levels of pro-inflammatory mediators like tumor necrosis factor-α (TNF-α); interleukins (ILs) like IL-6, IL-8, and IL-12; and C-reactive protein (CRP) in the sera and upregulated expression of protein kinase B phosphorylated at ser473 (pAKTser473)/nuclear factor-κB (NF-κB)/TNF-α axis in the leukocytes of exposed women with respect to control...
March 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28323187/activation-of-cytotoxic-natural-killer-cells-after-aneurysmal-subarachnoid-haemorrhage
#8
Daniel Spitzer, Nina Johanna Spitzer, Monika Deininger, Christian Rainer Wirtz, Ralph König, Timo Burster, Thomas Kapapa
OBJECTIVE: Cell-mediated inflammation is critical in development of cerebrovascular complications after aneurysmal subarachnoid haemorrhage (aSAH). We analysed the course for activated CD16(bright)CD56(dim) cytotoxic NKCSF cells (NK) in cerebrospinal fluid (CSF) of 15 patients. METHODS: Patients were classified by occurrence of cerebral vasospasm and delayed cerebral ischemia. NK were monitored by flow cytometry between day 1 and 14 after haemorrhage. RESULTS: 12 (80%) patients developed CV with a mean day of detection at 3...
March 16, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28321976/a-5-color-flow-cytometric-method-for-extended-8-part-leukocyte-differential
#9
Julien Guy, Orianne Wagner-Ballon, Olivier Pages, François Bailly, Jessica Borgeot, Marie-C Béné, Marc Maynadié
OBJECTIVES: Microscopic leukocyte differentials display many drawbacks. Several single 5 to 8-color tubes using multiparameter flow cytometry (MFC) are able to provide extended differentials with sequential gating-based analysis strategies. We investigated a new 5-color MFC method to perform an extended 8-part differential with a simplified gating strategy. METHODS: Whole blood was stained with a combination of antibodies including HLA-DR-FITC/CD19-PE/CD45-ECD/CD16-PC5+CD71-PC5/CD5-PC7...
March 21, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28321217/a-vaccine-therapy-for-canine-visceral-leishmaniasis-promoted-significant-improvement-of-clinical-and-immune-status-with-reduction-in-parasite-burden
#10
Bruno Mendes Roatt, Rodrigo Dian de Oliveira Aguiar-Soares, Levi Eduardo Soares Reis, Jamille Mirelle de Oliveira Cardoso, Fernando Augusto Siqueira Mathias, Rory Cristiane Fortes de Brito, Sydnei Magno da Silva, Nelder De Figueiredo Gontijo, Sidney de Almeida Ferreira, Jesus G Valenzuela, Rodrigo Corrêa-Oliveira, Rodolfo Cordeiro Giunchetti, Alexandre Barbosa Reis
Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#11
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320516/l-f001-a-novel-multifunctional-rock-inhibitor-suppresses-neuroinflammation-in-vitro-and-in-vivo-involvement-of-nf-%C3%AE%C2%BAb-inhibition-and-nrf2-pathway-activation
#12
Jingkao Chen, Wei Yin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
Microglia and astrocytes are largely responsible for inflammatory injury in the brain of Alzheimer's disease (AD). Increasing evidence has indicated that Rho kinase (ROCK) plays an important role in the regulation of neuroinflammation. Previously, we synthesized a new chemical entity L-F001 and proved its potential inhibitory effects on ROCK and oxidative stress. Here, we investigated the anti-inflammatory effects and the molecular mechanisms of L-F001 in vitro and in vivo. L-F001 remarkably suppressed lipopolysaccharides (LPS)-elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as LPS-induced production of nitric oxide (NO), reactive oxygen species, interleukin-6 (IL-6) and tumor necreactive oxygen speciesis factor-α (TNF-α) in microglial BV-2 cells and in cultured astrocytes...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28318628/b-and-t-cell-subpopulations-in-patients-with-severe-idiopathic-membranous-nephropathy-may-predict-an-early-response-to-rituximab
#13
Michelle Rosenzwajg, Eva Languille, Hanna Debiec, Joana Hygino, Karine Dahan, Tabassome Simon, David Klatzmann, Pierre Ronco
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56(bright)CD16(-/lo) NK subset...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28317806/mycobacterium-lepraemurium-uses-tlr-6-and-mr-but-not-lipid-rafts-or-dc-sign-to-gain-access-into-mouse-macrophages
#14
Mayra Silva-Miranda, Patricia Arce-Paredes, Oscar Rojas-Espinosa
OBJECTIVE/BACKGROUND: Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. MATERIALS AND METHODS: Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28293753/cd16-positive-circulating-monocytes-and-fibrotic-manifestations-of-systemic-sclerosis
#15
Alain Lescoat, Valérie Lecureur, Mikael Roussel, Béatrice Ly Sunnaram, Alice Ballerie, Guillaume Coiffier, Stéphane Jouneau, Olivier Fardel, Thierry Fest, Patrick Jégo
The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison...
March 14, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28293439/proteomic-analysis-of-hdac3-selective-inhibitor-in-the-regulation-of-inflammatory-response-of-primary-microglia
#16
Mingxu Xia, Qiuchen Zhao, He Zhang, Yanting Chen, Zengqiang Yuan, Yun Xu, Meijuan Zhang
HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28290822/-immunological-analysis-of-human-atherosclerotic-plaques-in-ex-vivo-culture-system
#17
D A Vorobyova, A M Lebedev, M S Vagida, O I Ivanova, E I Felker, V N Gontarenko, A V Shpektor, L B Margolis, E Yu Vasilieva
THE AIM OF THE STUDY: to analyze the dynamics of lymphocytic composition of human atherosclerotic plaques in ex vivo culture system. MATERIALS AND METHODS: The study included 15 atherosclerotic plaques obtained from patients who underwent carotid endarterectomy. Plaques were cultured as ring-shaped explants on collagen rafts in culture medium of special composition in CO2 incubator according to the previously developed technique. On day 0, and also on the 4th and 19th days of culture we extracted cells from plaque explants and analyzed B- and T-lymphocytic content of the tissue, as well as the percentage of CD16+ natural killer (NK) cells, using multichromatic flow cytometry...
December 2016: Kardiologiia
https://www.readbyqxmd.com/read/28289707/eomesodermin-and-t-bet-mark-developmentally-distinct-human-natural-killer-cells
#18
Amélie Collins, Nyanza Rothman, Kang Liu, Steven L Reiner
Immaturity of the immune system of human fetuses and neonates is often invoked to explain their increased susceptibility to infection; however, the development of the fetal innate immune system in early life remains incompletely explored. We now show that the most mature NK cells found in adult (or postnatal) human circulation (CD94(-)CD16(+)) are absent during ontogeny. Human fetal NK cells were found to express the 2 signature T-box transcription factors essential for the development of all murine NK and NK-like cells, eomesodermin (Eomes) and T-bet...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28286757/effect-of-tumor-necrosis-factor-inhibitor-therapy-on-osteoclasts-precursors-in-rheumatoid-arthritis
#19
Inês P Perpétuo, Joana Caetano-Lopes, Ana Maria Rodrigues, Raquel Campanilho-Marques, Cristina Ponte, Helena Canhão, Mari Ainola, João E Fonseca
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28284330/inhibition-of-ages-rage-rho-rock-pathway-suppresses-non-specific-neuroinflammation-by-regulating-bv2-microglial-m1-m2-polarization-through-the-nf-%C3%AE%C2%BAb-pathway
#20
Jingkao Chen, Zhaowei Sun, Minghua Jin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells...
April 15, 2017: Journal of Neuroimmunology
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