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Exhausted T cell

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https://www.readbyqxmd.com/read/27905100/the-severity-of-anaemia-depletes-cerebrovascular-dilatory-reserve-in-children-with-sickle-cell-disease-a-quantitative-magnetic-resonance-imaging-study
#1
Przemyslaw D Kosinski, Paula L Croal, Jackie Leung, Suzan Williams, Isaac Odame, Gregory M T Hare, Manohar Shroff, Andrea Kassner
Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) in children with SCD and to correlate these with haematological markers of anaemia...
December 1, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#2
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#3
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#4
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#5
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
November 24, 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27879553/acute-vision-loss-as-the-only-sign-of-leukemia-relapse
#6
Marta Cerdà-Ibáñez, Patricia Bayo-Calduch, Laura Manfreda-Domínguez, Antonio Duch-Samper
PURPOSE: To report a case of unilateral exudative retinal detachment as the sole presentation of relapsing B-type lymphoblastic leukemia in a 35-year-old man after 3 years of remission. METHODS: Case report. RESULTS: A 35-year-old man in complete remission of high-risk type B acute lymphoblastic leukemia (ALL-B) presented with acute vision loss in his left eye. Exudative retinal detachment was diagnosed at initial evaluation. Hematological and ocular studies were performed...
August 23, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27861555/p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#7
Susan Pereira Ribeiro, Jeffrey M Milush, Edecio Cunha-Neto, Esper G Kallas, Jorge Kalil, Luiz Felipe D Passero, Peter W Hunt, Steven G Deeks, Douglas F Nixon, Devi SenGupta
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls...
2016: PloS One
https://www.readbyqxmd.com/read/27853635/tumor-infiltrating-tim-3-t-cells-proliferate-avidly-except-when-pd-1-is-co-expressed-evidence-for-intracellular-cross-talk
#8
Jing Li, Gulidanna Shayan, Lyndsay Avery, Hyun-Bae Jie, Neil Gildener-Leapman, Nicole Schmitt, Bin Feng Lu, 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 highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27846930/-ccafu-french-national-guidelines-2016-2018-on-penile-cancer
#9
P Sèbe, L Ferretti, P-H Savoie, N Morel-Journel, A Fléchon, T Murez, L Rocher, P Camparo, A Méjean, X Durand
INTRODUCTION: The aim of this work is to establish guidelines proposed by the external genital organ group of the CCAFU for the diagnosis, treatment and follow-up of penile cancer. MATERIAL AND METHODS: The multidisciplinary working party studied 2013 guidelines exhaustively reviewed the literature, and evaluated references and their level of proof in order to attribute grades of recommandation. RESULTS: The most common histological type is squamous cell carcinoma...
November 2016: Progrès en Urologie
https://www.readbyqxmd.com/read/27846929/-ccafu-french-national-guidelines-2016-2018-on-testicular-germ-cell-tumors
#10
X Durand, A Fléchon, T Murez, L Rocher, P Camparo, N Morel-Journel, P-H Savoie, L Ferretti, P Sèbe, A Méjean
INTRODUCTION: The purpose of the oncologic comitee of the french association of urology was to establish guidelines proposed by the external genital organ group, for the diagnosis, treatment and follow-up of the germ cell tumours of the testis. MATERIAL AND METHODS: The multidisciplinary working group studied 2013 guidelines, exhaustively reviewed the literature, and evaluated references and their level of proof in order to attribute grades of recommandation. RESULTS: The initial workup of testicular cancer is based on clinical, laboratory (AFP, total hCG, LDH) and imaging assessment (scrotal ultrasound and chest, abdomen and pelvis computed tomography)...
November 2016: Progrès en Urologie
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
#11
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/27835012/observations-of-hall-reconnection-physics-far-downstream-of-the-x-line
#12
R Mistry, J P Eastwood, C C Haggerty, M A Shay, T D Phan, H Hietala, P A Cassak
Observations made using the Wind spacecraft of Hall magnetic fields in solar wind reconnection exhausts are presented. These observations are consistent with the generation of Hall fields by a narrow ion inertial scale current layer near the separatrix, which is confirmed with an appropriately scaled particle-in-cell simulation that shows excellent agreement with observations. The Hall fields are observed thousands of ion inertial lengths downstream from the reconnection X line, indicating that narrow regions of kinetic dynamics can persist extremely far downstream...
October 28, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27833058/basophil-mediated-pro-allergic-inflammation-in-vehicle-emitted-particles-exposure
#13
Alexander M Zakharenko, Ayse Basak Engin, Valery V Chernyshev, Vladimir V Chaika, Sergey M Ugay, Ramin Rezaee, Gholamreza Karimi, Vladimir A Drozd, Anna V Nikitina, Sergey F Solomennik, Olga R Kudryavkina, Liu Xin, Yuan Wenpeng, Manolis Tzatzarakis, Aristidis M Tsatsakis, Kirill S Golokhvast
Despite of the fact that engine manufacturers develop a new technology to reduce exhaust emissions, insufficient attention given to particulate emissions. However, diesel exhaust particles are a major source of air-borne pollution, contain vast amount of polycyclic aromatic hydrocarbons (PAHs) and may have deleterious effects on the immune system, resulting in the induction and enhancement of pro-allergic processes. In the current study, vehicle emitted particles (VEP) from 2 different types of cars (diesel - D and gasoline - G) and locomotive (L) were collected...
January 2017: Environmental Research
https://www.readbyqxmd.com/read/27829986/oxidative-stress-during-hiv-infection-mechanisms-and-consequences
#14
REVIEW
Alexander V Ivanov, Vladimir T Valuev-Elliston, Olga N Ivanova, Sergey N Kochetkov, Elizaveta S Starodubova, Birke Bartosch, Maria G Isaguliants
It is generally acknowledged that reactive oxygen species (ROS) play crucial roles in a variety of natural processes in cells. If increased to levels which cannot be neutralized by the defense mechanisms, they damage biological molecules, alter their functions, and also act as signaling molecules thus generating a spectrum of pathologies. In this review, we summarize current data on oxidative stress markers associated with human immunodeficiency virus type-1 (HIV-1) infection, analyze mechanisms by which this virus triggers massive ROS production, and describe the status of various defense mechanisms of the infected host cell...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27829019/subset-and-antigen-specific-effects-of-treg-on-cd8-t-cell-responses-in-chronic-hiv-infection
#15
Maria Nikolova, Aurélie Wiedemann, Maria Muhtarova, Daniela Achkova, Christine Lacabaratz, Yves Lévy
We, and others, have reported that in the HIV-negative settings, regulatory CD4+CD25highFoxP3+ T cells (Treg) exert differential effects on CD8 subsets, and maintain the memory / effector CD8+ T cells balance, at least in part through the PD-1/PD-L1 pathway. Here we investigated Treg-mediated effects on CD8 responses in chronic HIV infection. As compared to Treg from HIV negative controls (Treg/HIV-), we show that Treg from HIV infected patients (Treg/HIV+) did not significantly inhibit polyclonal autologous CD8+ T cell function indicating either a defect in the suppressive capacity of Treg/HIV+ or a lack of sensitivity of effector T cells in HIV infection...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27826124/-off-the-shelf-immunotherapy-with-ipsc-derived-rejuvenated-cytotoxic-t-lymphocytes
#16
Miki Ando, Hiromitsu Nakauchi
Adoptive T cell therapy to target and kill tumor cells shows promise and induces durable remissions in selected malignancies. However, for most cancers, clinical utility is limited. Cytotoxic T lymphocytes (CTLs) continuously exposed to viral or tumor antigens, with long-term expansion, may become unable to proliferate ("exhausted"). To exploit fully rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific CTLs is a potentially powerful approach. We review recent progress in engineering iPSC-derived T cells and prospects for clinical translation...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27825667/cell-intrinsic-barriers-of-t-cell-based-immunotherapy
#17
REVIEW
Hazem E Ghoneim, Anthony E Zamora, Paul G Thomas, Ben A Youngblood
Prolonged exposure of CD8(+) T cells to their cognate antigen can result in exhaustion of effector functions enabling the persistence of infected or transformed cells. Recent advances in strategies to rejuvenate host effector function using Immune Checkpoint Blockade have resulted in tremendous success towards the treatment of several cancers. However, it is unclear if T cell rejuvenation results in long-lived antitumor functions. Emerging evidence suggests that T cell exhaustion may also represent a significant impediment in sustaining long-lived antitumor activity by chimeric antigen receptor T cells...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#18
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27810927/scramblase-tmem16f-terminates-t-cell-receptor-signaling-to-restrict-t-cell-exhaustion
#19
Yu Hu, Ji Hyung Kim, Kangmin He, Qi Wan, Jessica Kim, Melanie Flach, Tom Kirchhausen, Andrea Vortkamp, Florian Winau
In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27809856/t-cells-in-multiple-myeloma-display-features-of-exhaustion-and-senescence-at-the-tumor-site
#20
Claudia Zelle-Rieser, Shanmugapriya Thangavadivel, Rainer Biedermann, Andrea Brunner, Patrizia Stoitzner, Ella Willenbacher, Richard Greil, Karin Jöhrer
BACKGROUND: Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments...
November 3, 2016: Journal of Hematology & Oncology
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