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Cell exhaustion

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https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#1
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456279/uncertainty-footprint-visualization-of-nonuniform-behavior-of-iterative-algorithms-applied-to-4d-cell-tracking
#2
Y Wan, C Hansen
Research on microscopy data from developing biological samples usually requires tracking individual cells over time. When cells are three-dimensionally and densely packed in a time-dependent scan of volumes, tracking results can become unreliable and uncertain. Not only are cell segmentation results often inaccurate to start with, but it also lacks a simple method to evaluate the tracking outcome. Previous cell tracking methods have been validated against benchmark data from real scans or artificial data, whose ground truth results are established by manual work or simulation...
June 2017: Computer Graphics Forum: Journal of the European Association for Computer Graphics
https://www.readbyqxmd.com/read/29455917/respiratory-hazard-assessment-of-combined-exposure-to-complete-gasoline-exhaust-and-respirable-volcanic-ash-in-a-multicellular-human-lung-model-at-the-air-liquid-interface
#3
Ines Tomašek, Claire J Horwell, Christoph Bisig, David E Damby, Pierre Comte, Jan Czerwinski, Alke Petri-Fink, Martin J D Clift, Barbara Drasler, Barbara Rothen-Rutishauser
Communities resident in urban areas located near active volcanoes can experience volcanic ash exposures during, and following, an eruption, in addition to sustained exposures to high concentrations of anthropogenic air pollutants (e.g., vehicle exhaust emissions). Inhalation of anthropogenic pollution is known to cause the onset of, or exacerbate, respiratory and cardiovascular diseases. It is further postulated similar exposure to volcanic ash can also affect such disease states. Understanding of the impact of combined exposure of volcanic ash and anthropogenic pollution to human health, however, remains limited...
February 15, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29449693/tumor-cell-intrinsic-tim-3-promotes-liver-cancer-via-nf-%C3%AE%C2%BAb-il-6-stat3-axis
#4
Hualin Zhang, Yang Song, Huimin Yang, Zhiyan Liu, Lifen Gao, Xiaohong Liang, Chunhong Ma
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449276/immune-evasion-via-pd-1-pd-l1-on-nk-cells-and-monocyte-macrophages-is-more-prominent-in-hodgkin-lymphoma-than-dlbcl
#5
Frank Vari, David Arpon, Colm Keane, Mark S Hertzberg, Dipti Talaulikar, Sanjiv Jain, Qingyan Cui, Erica Han, Josh Tobin, Robert Bird, Donna Cross, Annette Hernandez, Clare Gould, Simone Birch, Maher K Gandhi
Much focus has been on the interaction of PD-L1 on malignant B-cells with PD-1 on effector T-cells in inhibiting anti-lymphoma immunity. We sought to establish the contribution of NK-cells and inhibitory CD163 + monocytes/macrophages in Hodgkin Lymphoma (cHL) and Diffuse Large B-cell Lymphoma (DLBCL). Levels of PD-1 on NK-cells were elevated in cHL relative to DLBCL. Notably, CD3 - CD56 hi CD16 -ve NK-cells had substantially higher PD-1 expression relative to CD3 - CD56 dim CD16 + cells, and were expanded in blood and tissue, more marked in cHL than DLBCL patients...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29448937/engineering-chimeric-antigen-receptor-t-cells-for-cancer-treatment
#6
REVIEW
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29448857/therapy-free-remission-in-chronic-myeloid-leukemia-possible-mechanism
#7
Robert Peter Gale, Andreas Hochhaus
Chronic myeloid leukemia (CML) can be cured using tyrosine kinase-inhibitors (TKIs) when cure is defined as achieving a life-expectancy similar or even better than sex- and age-matched persons without CML. Most deaths in persons with CML are now from non-leukemia-related causes including heart disease, diabetes other cancers and stroke. Contrary to expectation, 40-50 percent of persons with CML treated for a few years with TKIs and who achieve a deep molecular response can stop TKI-therapy without leukemia recurrence for several years, some possibly indefinitely...
February 15, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29448156/improved-methane-removal-in-exhaust-gas-from-biogas-upgrading-process-using-immobilized-methane-oxidizing-bacteria
#8
Meng-Ting Sun, Zhi-Man Yang, Shan-Fei Fu, Xiao-Lei Fan, Rong-Bo Guo
Methane in exhaust gas from biogas upgrading process, which is a greenhouse gas, could cause global warming. The biofilter with immobilized methane-oxidizing bacteria (MOB) is a promising approach for methane removal, and the selections of inoculated MOB culture and support material are vital for the biofilter. In this work, five MOB consortia were enriched at different methane concentrations. The MOB-20 consortium enriched at the methane concentration of 20.0% (v/v) was then immobilized on sponge and two particle sizes of volcanic rock in biofilters to remove methane in exhaust gas from biogas upgrading process...
February 7, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#9
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29444930/immunophenotyping-of-newly-diagnosed-and-recurrent-glioblastoma-defines-distinct-immune-exhaustion-profiles-in-peripheral-and-tumor-infiltrating-lymphocytes
#10
Malte Mohme, Simon Schliffke, Cecile L Maire, Alessandra Rünger, Laura Glau, Klaus C Mende, Jakob Matschke, Christina Gehbauer, Nuray Akyüz, Svenja Zapf, Mareike Holz, Miriam Schaper, Tobias Martens, Nils O Schmidt, Sven Peine, Manfred Westphal, Mascha Binder, Eva Tolosa, Katrin Lamszus
PURPOSE: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T-cells (TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion. EXPERIMENTAL DESIGN: We used flow-cytometry and cytokine assays to profile TILs and blood lymphocytes (PBL) from GBM patients, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444704/hpmsc-transplantation-restoring-ovarian-function-in-premature-ovarian-failure-mice-is-associated-with-change-of-th17-tc17-and-th17-treg-cell-ratios-through-the-pi3k-akt-signal-pathway
#11
Na Yin, Yanlin Wang, Xueyan Lu, Ranran Liu, Lianshuang Zhang, Wei Zhao, Wendan Yuan, Qianqian Luo, Hao Wu, Xiying Luan, Hongqin Zhang
BACKGROUND: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation...
February 14, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29444341/high-fat-diet-induced-obesity-promotes-expansion-of-bone-marrow-adipose-tissue-and-impairs-skeletal-stem-cell-functions-in-mice
#12
Michaela Tencerova, Florence Figeac, Nicholas Ditzel, Hanna Taipaleenmäki, Tina Kamilla Nielsen, Moustapha Kassem
Obesity represents a risk factor for development of insulin resistance and Type 2 Diabetes. In addition, it has been associated with increased adipocyte formation in the bone marrow (BM) along with increased risk for bone fragility fractures. However, little is known on the cellular mechanisms that link obesity, BM adiposity and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with high fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells and BM microenvironment in comparison to peripheral adipose tissue (AT)...
February 14, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29444128/molecular-action-of-isoflavone-genistein-in-the-human-epithelial-cell-line-hacat
#13
Elwira Smolińska, Marta Moskot, Joanna Jakóbkiewicz-Banecka, Grzegorz Węgrzyn, Bogdan Banecki, Aneta Szczerkowska-Dobosz, Dorota Purzycka-Bohdan, Magdalena Gabig-Cimińska
Due to its strong proliferation-reducing effects on keratinocytes, and also anti-inflammatory properties, the isoflavone genistein has already been proposed as a possible antipsoriatic compound. As there is still no detailed information on this topic, we examined the effects of genistein by using an in vitro model of both, normal and "psoriasis-like" keratinocytes at this stage of our work exhaustively testing the selected flavonoid in a mono-treated experimental design. Gene expression studies revealed transcriptional changes that confirms known disease-associated pathways and highlights many psoriasis-related genes...
2018: PloS One
https://www.readbyqxmd.com/read/29444087/safety-and-efficacy-of-anti-pd-l1-therapy-in-the-woodchuck-model-of-hbv-infection
#14
Scott Balsitis, Volodymyr Gali, Pamela J Mason, Susan Chaniewski, Steven M Levine, Michael J Wichroski, Michael Feulner, Yunling Song, Karen Granaldi, James K Loy, Chris M Thompson, Jacob A Lesniak, Catherine Brockus, Narendra Kishnani, Stephan Menne, Mark I Cockett, Renuka Iyer, Stephen W Mason, Daniel J Tenney
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters...
2018: PloS One
https://www.readbyqxmd.com/read/29441645/short-telomeres-induce-p53-and-autophagy-and-modulate-age-associated-changes-in-cardiac-progenitor-cell-fate
#15
Collin Matsumoto, Yan Jiang, Jacqueline Emathinger, Pearl Quijada, Nathalie Nguyen, Andrea De La Torre, Maryam Moshref, Jonathan Nguyen, Aimee B Levinson, Minyoung Shin, Mark A Sussman, Nirmala Hariharan
Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis and senescence, as compared to common lab strains FVB and C57 bearing longer telomeres...
February 14, 2018: Stem Cells
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#16
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29432896/transcriptional-response-to-organic-compounds-from-diverse-gasoline-and-biogasoline-fuel-emissions-in-human-lung-cells
#17
Helena Libalova, Pavel Rossner, Kristyna Vrbova, Tana Brzicova, Jitka Sikorova, Michal Vojtisek-Lom, Vit Beranek, Jiri Klema, Miroslav Ciganek, Jiri Neca, Miroslav Machala, Jan Topinka
Modern vehicles equipped with Gasoline Direct Injection (GDI) engine have emerged as an important source of particulate emissions potentially harmful to human health. We collected and characterized gasoline exhaust particles (GEPs) produced by neat gasoline fuel (E0) and its blends with 15% ethanol (E15), 25% n-butanol (n-But25) and 25% isobutanol (i-But25). To study the toxic effects of organic compounds extracted from GEPs, we analyzed gene expression profiles in human lung BEAS-2B cells. Despite the lowest GEP mass, n-But25 extract contained the highest concentration of polycyclic aromatic hydrocarbons (PAHs), while i-But25 extract the lowest...
February 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29427415/ccr8-expression-defines-tissue-resident-memory-t-cells-in-human-skin
#18
Michelle L McCully, Kristin Ladell, Robert Andrews, Rhiannon E Jones, Kelly L Miners, Laureline Roger, Duncan M Baird, Mark J Cameron, Zita M Jessop, Iain S Whitaker, Eleri L Davies, David A Price, Bernhard Moser
Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8- skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1)...
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29425473/beetroot-increases-muscle-performance-and-oxygenation-during-sustained-isometric-exercise-but-does-not-alter-muscle-oxidative-efficiency-and-microvascular-reactivity-at-rest
#19
Stavros Papadopoulos, Konstantina Dipla, Areti Triantafyllou, Michalis G Nikolaidis, Antonios Kyparos, Panagiota Touplikioti, Ioannis S Vrabas, Andreas Zafeiridis
OBJECTIVE: To examine the effects of beetroot juice (BRJ) on (i) in vivo skeletal muscle O2 consumption (mVO2) and microvascular reactivity at rest and (ii) muscle performance, muscle oxygenation, and mVO2 during sustained isometric handgrip exercise (IHG). METHODS: Sixteen young males consumed, randomly, a nitrate-rich (8.1 mmol BRJnitrate) or nitrate-depleted (BRJplacebo) BRJ. After 2.5 hours, they performed an occlusion-reperfusion maneuver at rest, a 3-minute sustained IHG, and a sustained IHG to exhaustion with arterial occlusion...
February 9, 2018: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/29422056/turning-the-tables-on-cytomegalovirus-targeting-viral-fc-receptors-by-cars-containing-mutated-ch2-ch3-igg-spacer-domains
#20
Julia Proff, Charlotte U Brey, Armin Ensser, Wolfgang Holter, Manfred Lehner
BACKGROUND: During infection with human cytomegalovirus (HCMV) several viral proteins occur on cell surfaces in high quantity. We thus pursue an HLA-independent approach for immunotherapy of HCMV using chimeric antigen receptors (CARs) and bispecific BiTE® antibody constructs. In this context, HCMV-encoded proteins that mediate viral immune evasion and bind human IgG might represent particularly attractive target antigens. Unlike in observations of similar approaches for HIV and hepatitis B and C viruses, however, HCMV-infected cells develop a striking resistance to cytotoxic effector functions at later stages of the replication cycle...
February 8, 2018: Journal of Translational Medicine
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