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https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#1
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/28205538/complement-component-5-promotes-lethal-thrombosis
#2
Tomohiro Mizuno, Kengo Yoshioka, Masashi Mizuno, Mie Shimizu, Fumihiko Nagano, Tomoyuki Okuda, Naotake Tsuboi, Shoichi Maruyama, Tadashi Nagamatsu, Masaki Imai
Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45-75 μg/g)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#3
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198713/cd1d-restricted-natural-killer-t-cells-are-preserved-in-indian-long-term-non-progressors-ltnps
#4
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
BACKGROUND: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. METHODOLOGY: NKT cells were characterized for their frequency and the activation, aging, exhaustion status and their proliferation ability in 32 long term non progressors (LTNPs), 40 progressors, 18 patients before and after suppressive cART along with 35 HIV-1 negative subjects using multicolor flowcytometry...
February 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28197778/evaluating-effects-of-l-carnitine-on-human-bone-marrow-derived-mesenchymal-stem-cells
#5
Koichi Fujisawa, Taro Takami, Yumi Fukui, Luiz Fernando Quintanilha, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
Mesenchymal stem cells (MSCs) are multipotent cells showing potential for use in regenerative medicine. Culture techniques that are more stable and methods for the more efficient production of MSCs with therapeutic efficacy are needed. We evaluate the effects of growing bone marrow (Bm)-derived MSCs in the presence of L-carnitine, which is believed to promote lipid metabolism and to suppress apoptosis. The presence of L-carnitine decreased the degree of drug-induced apoptosis and suppressed adipogenic differentiation...
February 14, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#6
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#7
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#8
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#9
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28193736/down-regulation-of-cd73-on-b-cells-of-patients-with-viremic-hiv-correlates-with-b-cell-activation-and-disease-progression
#10
Eun-Seong Kim, Christin Ackermann, Ilona Tóth, Patrick Dierks, Johanna M Eberhard, Raluca Wroblewski, Felix Scherg, Matthias Geyer, Reinhold E Schmidt, Claudia Beisel, Maximilian Bockhorn, Friedrich Haag, Jan van Lunzen, Julian Schulze Zur Wiesch
Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0...
February 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28192087/endothelial-cell-markers-from-clinician-s-perspective
#11
REVIEW
Jelena Rakocevic, Dejan Orlic, Olivera Mitrovic-Ajtic, Miloje Tomasevic, Milan Dobric, Natasa Zlatic, Dejan Milasinovic, Goran Stankovic, Miodrag Ostojić, Milica Labudovic-Borovic
Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine...
February 9, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28191781/direct-isolation-and-characterization-of-human-nephron-progenitors
#12
Stefano Da Sacco, Matthew E Thornton, Astgik Petrosyan, Maria Lavarreda-Pearce, Sargis Sedrakyan, Brendan H Grubbs, Roger E De Filippo, Laura Perin
Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28179496/cutting-edge-chromatin-accessibility-programs-cd8-t-cell-memory
#13
Christopher D Scharer, Alexander P R Bally, Bhanu Gandham, Jeremy M Boss
CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28178980/novel-neuro-audiological-findings-and-further-evidence-for-twnk-involvement-in-perrault-syndrome
#14
Monika Ołdak, Dominika Oziębło, Agnieszka Pollak, Iwona Stępniak, Michal Lazniewski, Urszula Lechowicz, Krzysztof Kochanek, Mariusz Furmanek, Grażyna Tacikowska, Dariusz Plewczynski, Tomasz Wolak, Rafał Płoski, Henryk Skarżyński
BACKGROUND: Hearing loss and ovarian dysfunction are key features of Perrault syndrome (PRLTS) but the clinical and pathophysiological features of hearing impairment in PRLTS individuals have not been addressed. Mutations in one of five different genes HSD17B4, HARS2, LARS2, CLPP or TWNK (previous symbol C10orf2) cause the autosomal recessive disorder but they are found only in about half of the patients. METHODS: We report on two siblings with a clinical picture resembling a severe, neurological type of PRLTS...
February 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#15
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28174316/density-dependent-recycling-promotes-the-long-term-survival-of-bacterial-populations-during-periods-of-starvation
#16
Sotaro Takano, Bogna J Pawlowska, Ivana Gudelj, Tetsuya Yomo, Saburo Tsuru
: The amount of natural resources in the Earth's environment is in flux, which can trigger catastrophic collapses of ecosystems. How populations survive under nutrient-poor conditions is a central question in ecology. Curiously, some bacteria persist for a long time in nutrient-poor environments. Although this survival may be accomplished through cell death and the recycling of dead cells, the importance of these processes and the mechanisms underlying the survival of the populations have not been quantitated...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28170385/exhausting-alloreactivity-of-donor-derived-car-t-cells
#17
Maksim Mamonkin, Helen E Heslop
No abstract text is available yet for this article.
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28165481/targeting-mitochondrial-dysfunction-can-restore-antiviral-activity-of-exhausted-hbv-specific-cd8-t-cells-in-chronic-hepatitis-b
#18
Paola Fisicaro, Valeria Barili, Barbara Montanini, Greta Acerbi, Manuela Ferracin, Francesca Guerrieri, Debora Salerno, Carolina Boni, Marco Massari, M Cristina Cavallo, Glenda Grossi, Tiziana Giuberti, Pietro Lampertico, Gabriele Missale, Massimo Levrero, Simone Ottonello, Carlo Ferrari
Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28165049/new-insights-into-the-electrochemical-behavior-of-acid-orange-7-convergent-paired-electrochemical-synthesis-of-new-aminonaphthol-derivatives
#19
Shima Momeni, Davood Nematollahi
Electrochemical behavior of acid orange 7 has been exhaustively studied in aqueous solutions with different pH values, using cyclic voltammetry and constant current coulometry. This study has provided new insights into the mechanistic details, pH dependence and intermediate structure of both electrochemical oxidation and reduction of acid orange 7. Surprisingly, the results indicate that a same redox couple (1-iminonaphthalen-2(1H)-one/1-aminonaphthalen-2-ol) is formed from both oxidation and reduction of acid orange 7...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163249/activation-and-exhaustion-of-antigen-specific-cd8-t-cells-occur-in-different-splenic-compartments-during-infection-with-plasmodium-berghei
#20
Ganchimeg Bayarsaikhan, Mana Miyakoda, Kazuo Yamamoto, Daisuke Kimura, Masoud Akbari, Masao Yuda, Katsuyuki Yui
The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8(+) T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8(+) T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection...
February 3, 2017: Parasitology International
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