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PD-1 B cell

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https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#1
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28639391/an-investigation-of-the-relationship-between-recurrent-spontaneous-abortion-and-memory-t-follicular-helper-cells
#2
Xiaorui Luan, Xiaomin Kang, Weiping Li, Qian Dong
PROBLEM: Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. METHODS OF STUDY: Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination...
June 21, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28637884/vaccination-establishes-clonal-relatives-of-germinal-center-t-cells-in-the-blood-of-humans
#3
Antje Heit, Frank Schmitz, Sarah Gerdts, Britta Flach, Miranda S Moore, Jonathan A Perkins, Harlan S Robins, Alan Aderem, Paul Spearman, Georgia D Tomaras, Stephen C De Rosa, M Juliana McElrath
Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5(+)CD4(+) Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28637670/a-randomised-double-blind-trial-to-demonstrate-bioequivalence-of-gp2013-and-reference-rituximab-combined-with-methotrexate-in-patients-with-active-rheumatoid-arthritis
#4
Josef S Smolen, Stanley B Cohen, Hans-Peter Tony, Morton Scheinberg, Alan Kivitz, Andra Balanescu, Juan Gomez-Reino, Liyi Cen, Peijuan Zhu, Tamas Shisha
OBJECTIVES: The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment. METHODS: In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid...
June 21, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#5
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28634551/mechanisms-and-consequences-of-dopamine-depletion-induced-attenuation-of-the-spinophilin-neurofilament-medium-interaction
#6
Andrew C Hiday, Michael C Edler, Asma B Salek, Cameron W Morris, Morrent Thang, Tyler J Rentz, Kristie L Rose, Lisa M Jones, Anthony J Baucum
Signaling changes that occur in the striatum following the loss of dopamine neurons in the Parkinson disease (PD) are poorly understood. While increases in the activity of kinases and decreases in the activity of phosphatases have been observed, the specific consequences of these changes are less well understood. Phosphatases, such as protein phosphatase 1 (PP1), are highly promiscuous and obtain substrate selectivity via targeting proteins. Spinophilin is the major PP1-targeting protein enriched in the postsynaptic density of striatal dendritic spines...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28633555/glutamine-administration-in-early-or-late-septic-phase-downregulates-lymphocyte-pd-1-pd-l1-expression-and-the-inflammatory-response-in-mice-with-polymicrobial-sepsis
#7
Ya-Mei Hu, Yuan-Chin Hsiung, Man-Hui Pai, Sung-Ling Yeh
BACKGROUND: Sepsis is a severe inflammatory response to infection. Excessive compensation to inflammation leads to dysregulated immune response that ultimately results in organ damage and lethality of sepsis. This study administered glutamine (GLN) in the early or late phase of sepsis to investigate its effects on regulating leukocyte programmed cell death 1 (PD-1) and its ligand (programmed cell death ligand 1 [PD-L1]) expression, macrophage function, inflammation, and acute kidney injury in sepsis...
March 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#8
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#9
Laetitia Laurent, Awena Lefur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic Lupus Erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28629895/tumour-suppressor-micrornas-contribute-to-the-regulation-of-pd-l1-expression-in-malignant-pleural-mesothelioma
#10
Steven C Kao, Yuen Yee Cheng, Marissa Williams, Michaela B Kirschner, Jason Madore, Trina Lum, Kadir H Sarun, Anthony Linton, Brian McCaughan, Sonja Klebe, Nico van Zandwijk, Richard A Scolyer, Michael J Boyer, Wendy A Cooper, Glen Reid
INTRODUCTION: The upregulation of PD-L1 is found in many cancers and contributes to the evasion of the host's immune defence. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with non-epithelioid histological subtype and poor prognosis, but the pathways involved in the control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression...
June 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#11
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28627735/genetic-alterations-in-adult-t-cell-leukemia-lymphoma
#12
REVIEW
Yasunori Kogure, Keisuke Kataoka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with a dismal prognosis, caused by human T-cell leukemia virus type-1 (HTLV-1) retrovirus. A long latency period from HTLV-1 infection to ATL onset suggests that not only HTLV-1 proteins, such as Tax and HBZ, but also additional genetic and/or epigenetic events are required for ATL development. Although many studies have demonstrated the biological functions of viral genes, alterations of cellular genes associated with ATL have not been fully investigated...
June 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28622456/elevated-ccl25-and-ccr9-expressing-t-helper-cells-in-salivary-glands-of-primary-sj%C3%A3-gren-s-syndrome-patients-potential-new-axis-in-lymphoid-neogenesis
#13
Sofie L M Blokland, Maarten R Hillen, Aike A Kruize, Stephan Meller, Bernhard Homey, Glennda M Smithson, Timothy R D J Radstake, Joel A G van Roon
Introduction T follicular helper (Tfh)-cells play a critical role in germinal center formation and B-cell activation, both hallmarks of primary Sjögren's syndrome (pSS). CCR9-expressing Th-cells have "Tfh-like" characteristics and are increased at mucosa-associated sites in several inflammatory conditions. Because of their unique characteristics and limited evaluation we investigated the local and systemic CCL25/CCR9-axis in pSS. Methods CCL25 protein and mRNA levels and CCR9+ Th-cells were assessed in labial salivary glands (LSG) of pSS and non-Sjögren's sicca (nSS) patients and their correlation with inflammatory and clinical parameters was evaluated...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#14
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611636/autoimmune-diabetes-and-thyroiditis-complicating-treatment-with-nivolumab
#15
Li Li, Awais Masood, Shahla Bari, Sahzene Yavuz, Alan B Grosbach
Programmed cell death-1 (PD-1) ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#16
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28611304/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#17
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611299/cblb-deficient-t-cells-are-less-susceptible-to-pd-l1-mediated-inhibition
#18
Sebastian Peer, Gottfried Baier, Thomas Gruber
Modulation of the immune system for the treatment of primary and metastatic tumors has been a goal of cancer research for many years. The E3 ubiquitin ligase Cbl-b has been established as an intracellular checkpoint that limits T cell activation, critically contributing to the maintenance of self-tolerance. Furthermore, it has been shown that Cblb deficiency enhances T cell effector functions towards tumors. Blockade of the immune checkpoints CTLA-4 and PD-1/PD-L1 has recently emerged as a promising strategy in the development of effective cancer immune therapies...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609832/pembrolizumab-induced-thyroiditis-comprehensive-clinical-review-and-insights-into-underlying-involved-mechanisms
#19
Danae A Delivanis, Michael P Gustafson, Svetlana Bornschlegl, Michele M Merten, Lisa Kottschade, Sarah Withers, Allan B Dietz, Mabel Ryder
Context: Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1 induced thyroid irAEs. Design: Single center, retrospective cohort study. Patients and Measurements: We studied 93 patients with advanced cancer (aged 24–82 years; 60% males) who received at least one infusion of pembrolizumab...
May 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28605599/stat3-induces-immunosuppression-by-upregulating-pd-1-pd-l1-in-hnscc
#20
L L Bu, G T Yu, L Wu, L Mao, W W Deng, J F Liu, A B Kulkarni, W F Zhang, L Zhang, Z J Sun
Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections...
June 1, 2017: Journal of Dental Research
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