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Exhausted T cell

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https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#1
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#2
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28716576/tlr9-mediated-conditioning-of-liver-environment-is-essential-for-successful-intrahepatic-immunotherapy-and-effective-memory-recall
#3
Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Ramona F Kratzer, Florian Kreppel, Georgia Koutsoumpli, Toos Daemen, Hansjörg Hauser, Dagmar Wirth
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients...
July 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28715493/host-genetics-play-a-critical-role-in-controlling-cd8-t-cell-function-and-lethal-immunopathology-during-chronic-viral-infection
#4
Allison F Christiaansen, Megan E Schmidt, Stacey M Hartwig, Steven M Varga
Effective CD8 T cell responses are vital for the control of chronic viral infections. Many factors of the host immune response contribute to the maintenance of effector CD8 T cell responses versus CD8 T cell exhaustion during chronic infection. Specific MHC alleles and the degree of MHC heterogeneity are associated with enhanced CD8 T cell function and viral control during human chronic infection. However, it is currently unclear to what extent host genetics influences the establishment of chronic viral infection...
July 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28713869/association-of-anisocytosis-with-markers-of-immune-activation-and-exhaustion-in-treated-hiv
#5
Sadeer G Al-Kindi, David A Zidar, Grace A McComsey, Chris T Longenecker
BACKGROUND: Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy. METHODS: We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28710491/ageing-and-latent-cmv-infection-impact-on-maturation-differentiation-and-exhaustion-profiles-of-t-cell-receptor-gammadelta-t-cells
#6
Martine J Kallemeijn, Anne Mieke H Boots, Michèle Y van der Klift, Elisabeth Brouwer, Wayel H Abdulahad, Jan A N Verhaar, Jacques J M van Dongen, Anton W Langerak
Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#7
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28707699/predict-disease-progression-from-t-cell-phenotypes-in-northern-pig-tailed-macaques-macaca-leonina-during-sivmac239-infection
#8
Ming-Xu Zhang, Hong-Yi Zheng, Jin Jiang, Jia-Hao Song, Min Chen, Yu Xiao, Xiao-Dong Lian, Tian-Zhang Song, Ren-Rong Tian, Wei Pang, Yong-Tang Zheng
Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analyzed, for the first time, the correlations between T cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T cell count, CD4/CD8 ratio and lower plasma viral load than NPs. CD4+ T cell count and CD4/CD8 ratio decreased more sharply in NPs than in SPs...
July 14, 2017: Immunology
https://www.readbyqxmd.com/read/28696685/modeling-sequence-dependent-peptide-fluctuations-in-immunologic-recognition
#9
Cory M Ayres, Timothy P Riley, Steven A Corcelli, Brian M Baker
In cellular immunity, T cells recognize peptide antigens bound and presented by major histocompatibility complex (MHC) proteins. The motions of peptides bound to MHC play a significant role in determining immunogenicity. However, existing approaches for investigating peptide/MHC motional dynamics are challenging or of low throughput, hindering the development of algorithms for predicting immunogenicity from large databases, such as those of tumor or genetically unstable viral genomes. We addressed this by performing exhaustive molecular dynamics simulations on a large structural database of peptides bound to the most commonly expressed human class I MHC protein, HLA-A*0201...
July 11, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28692589/emerging-cancer-specific-therapeutic-aptamers
#10
Sorah Yoon, John J Rossi
PURPOSE OF REVIEW: We will describe recently discovered smart aptamers with tumor specificity, with an emphasis on targeted delivery of novel therapeutic molecules, cancer-specific biomarkers, and immunotherapy. RECENT FINDINGS: The development of cancer-specific aptamers has facilitated targeted delivery of potent therapeutic molecules to cancer cells without harming nontumoral cells. This specificity also makes it possible to discover novel cancer biomarkers. Furthermore, alternative immune-checkpoint blockade aptamers have been developed for combinational immunotherapy...
July 7, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28692536/asymptomatic-anorectal-chlamydia-trachomatis-and-neisseria-gonorrhoeae-infections-are-associated-with-systemic-cd8-t-cell-activation
#11
Vinicius A Vieira, Vivian I Avelino-Silva, Natalia B Cerqueira, Dayane A Costa, Priscilla R Costa, Ricardo P Vasconcelos, Valdez R Madruga, Ronaldo Ismério Moreira, Brenda Hoagland, Valdiléa G Veloso, Beatriz Grinsztejn, Esper G Kallás
BACKGROUND: Oral pre-exposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T cell activation is a risk factor for sexually acquired HIV-1 infection...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28690843/the-role-of-pd-1-in-regulation-of-macrophage-apoptosis-and-its-subversion-by-leishmania-donovani
#12
Shalini Roy, Purnima Gupta, Shreyasi Palit, Moumita Basu, Anindita Ukil, Pijush K Das
Programmed death-1 receptor (PD-1) expressed in many immune cells is known to trigger T-cell exhaustion but the significance of macrophage-associated PD-1 in relevance to macrophage apoptosis is not known. This study is aimed to delineate whether PD-1 pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, Leishmania donovani modulates PD-1 pathway for protecting its niche. Resting macrophages when treated with H2O2 showed increased PD-1 expression and apoptosis, which was further enhanced on PD-1 agonist treatment...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28687491/site-specific-regulation-of-oral-mucosa-recruiting-cd8-t-cells-in-a-mouse-contact-allergy-model
#13
Worawalun Hirunwidchayarat, Emi Furusawa, Siwen Kang, Tatsukuni Ohno, Shunsuke Takeuchi, Sorasun Rungsiyanont, Miyuki Azuma
Contact allergy is a T cell-mediated, delayed-type hypersensitivity generated by contact exposure of an allergen to the skin and mucosal surface. The clinical manifestations of allergic responses between the skin and oral mucosa vary and the differences in immunopathology have not been clarified. We generated hapten-induced contact hypersensitivity (CH) of the buccal mucosa (BM) in parallel studies with ear skin (ES) CH, and observed several characteristic findings of BM CH. The BM challenge induced more rapid and more severe inflammation than the ES challenge, with abundant granulocyte and CD8(+) T cell infiltration...
July 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28681703/hybrid-approach-to-model-the-spatial-regulation-of-t-cell-responses
#14
Anass Bouchnita, Gennady Bocharov, Andreas Meyerhans, Vitaly Volpert
BACKGROUND: Moving from the molecular and cellular level to a multi-scale systems understanding of immune responses requires the development of novel approaches to integrate knowledge and data from different biological levels into mechanism-based integrative mathematical models. The aim of our study is to present a methodology for a hybrid modelling of immunological processes in their spatial context. METHODS: A two-level hybrid mathematical model of immune cell migration and interaction integrating cellular and organ levels of regulation for a 2D spatial consideration of idealized secondary lymphoid organs is developed...
June 21, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28680755/bispecific-antibody-does-not-induce-t-cell-death-mediated-by-chimeric-antigen-receptor-against-disialoganglioside-gd2
#15
Sayed Shahabuddin Hoseini, Konstantin Dobrenkov, Dmitry Pankov, Xiaoliang L Xu, Nai-Kong V Cheung
Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CAR-modified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679488/toward-a-new-kind-of-vaccine-a-logical-extension-of-the-symmetrical-immune-network-theory
#16
Reginald Gorczynski, Geoffrey Hoffmann
BACKGROUND: The symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies. OBJECTIVE: The aim of this study was to confirm the existence of specific T cells factors and to show that immunization of C3H mice with BL/6 skin or using nominal antigen for immunization (Tetanus Toxoid) induced production of antigen-specific (anti-BL/6 or antitetanus) antibodies plus anti-idiotypic antibodies (C3H anti-anti-C3H)...
July 5, 2017: Interactive Journal of Medical Research
https://www.readbyqxmd.com/read/28674062/mitochondrial-toxicity-of-linezolid-in-blood-cells-and-skin-nerve-fibers-influence-of-mitochondrial-genetics
#17
G Garrabou, À Soriano, T Pinós, J Casanova-Mollà, D Pacheu-Grau, C Morén, E García-Arumí, M Morales, E Ruiz-Pesini, M Catalán-Garcia, J C Milisenda, E Lozano, A L Andreu, J Montoya, J Mensa, F Cardellach
Background: The antibiotic linezolid is a ribosomal inhibitor with excellent efficacy. Despite reduction in the administration period to 28 days, side effects usually of hematologic or neuropathic origin are still reported due to secondary inhibition of mitochondrial protein synthesis. Susceptibility to linezolid toxicity remains unknown.Objective: To understand clinical heterogenicity in response to identical linezolid exposition through the exhaustive examination of the molecular basis of tissue-dependent mitotoxicity, derived cell dysfunction and mitochondrial genetic association to adverse effects of linezolid under the recommended period of administration...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#18
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28671989/tnf-signalling-drives-expansion-of-bone-marrow-cd4-t-cells-responsible-for-hsc-exhaustion-in-experimental-visceral-leishmaniasis
#19
Ana Isabel Pinto, Najmeeyah Brown, Olivier Preham, Johannes S P Doehl, Helen Ashwin, Paul M Kaye
Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28670966/malnutrition-in-hiv-infected-children-is-an-indicator-of-severe-disease-with-an-impaired-response-to-antiretroviral-therapy
#20
Maximilian Muenchhoff, Michael Healy, Ravesh Singh, Julia Roider, Andreas Groll, Chirjeev Kindra, Thobekile Sibaya, Angeline Moonsamy, Callum McGregor, Michelle Q Phan, Alejandro Palma, Henrik Kloverpris, Alasdair Leslie, Raziya Bobat, Philip S LaRussa, Thumbi Ndung'u, Philip Jr Goulder, Magdalena E Sobieszczyk, Mohendran Archary
Objectives This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. Design We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM...
July 2, 2017: AIDS Research and Human Retroviruses
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