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EBV T cells

Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Austen J J Worth, Charlotte J Houldcroft, Claire Booth
Epstein-Barr virus (EBV) infection is ubiquitous in humans, but the majority of infections have an asymptomatic or self-limiting clinical course. Rarely, individuals may develop a pathological EBV infection with a variety of life threatening complications (including haemophagocytosis and malignancy) and others develop asymptomatic chronic EBV viraemia. Although an impaired ability to control EBV infection has long been recognised as a hallmark of severe T-cell immunodeficiency, the advent of next generation sequencing has identified a series of Primary Immunodeficiencies in which EBV-related pathology is the dominant feature...
October 17, 2016: British Journal of Haematology
Xi-Wen Bi, Hua Wang, Wen-Wen Zhang, Jing-Hua Wang, Wen-Jian Liu, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. METHODS: Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively...
October 13, 2016: Journal of Hematology & Oncology
Shotaro Ando, Jun-Ichi Kawada, Takahiro Watanabe, Michio Suzuki, Yoshitaka Sato, Yuka Torii, Masato Asai, Fumi Goshima, Takayuki Murata, Norio Shimizu, Yoshinori Ito, Hiroshi Kimura
Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model...
October 8, 2016: Oncotarget
Yuki Komabayashi, Kan Kishibe, Toshihiro Nagato, Seigo Ueda, Miki Takahara, Yasuaki Harabuchi
Nasal natural killer/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and is characterized by local invasion and widespread dissemination, with a consequent poor prognosis. Micro-RNAs (miRNAs) play roles in the pathogenesis of several malignancies by regulating gene expression and have been recently identified as stable entities in serum. Here, we investigated the value of circulating EBV-miRNAs as biomarkers for NNKTL. Sera of patients with NNKTL were subjected to miRNA polymerase chain reaction (PCR)-array analysis, after which serum EBV-miRNA levels were verified using quantitative PCR...
October 6, 2016: Hematological Oncology
Manuel Albanese, Takanobu Tagawa, Mickaël Bouvet, Liridona Maliqi, Dominik Lutter, Jonathan Hoser, Maximilian Hastreiter, Mitch Hayes, Bill Sugden, Larissa Martin, Andreas Moosmann, Wolfgang Hammerschmidt
Infection with Epstein-Barr virus (EBV) affects most humans worldwide and persists life-long in the presence of robust virus-specific T-cell responses. In both immunocompromised and some immunocompetent people, EBV causes several cancers and lymphoproliferative diseases. EBV transforms B cells in vitro and encodes at least 44 microRNAs (miRNAs), most of which are expressed in EBV-transformed B cells, but their functions are largely unknown. Recently, we showed that EBV miRNAs inhibit CD4(+) T-cell responses to infected B cells by targeting IL-12, MHC class II, and lysosomal proteases...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mahua Sinha, Clementina Rama Rao, C S Premalata, Mohammed Shafiulla, K C Lakshmaiah, Linu Abraham Jacob, Govind K Babu, B K Viveka, L Appaji, Jayshree R Subramanyam
CONTEXT: There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. AIMS: The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL)...
July 2016: Indian Journal of Medical and Paediatric Oncology
Amber Shatzer, Mir A Ali, Mayra Chavez, Kennichi Dowdell, Min-Jung Lee, Yusuke Tomita, Iman El-Hariry, Jane B Trepel, David A Proia, Jeffrey I Cohen
HSP90 inhibitors have been shown to kill Epstein-Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line...
August 11, 2016: Leukemia & Lymphoma
Li Zhang, Na Li, Li Yang, Jing Zhang, Hua-Wei Weng, Li-Qun Zou
B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells...
December 2016: Cytokine
Colm Keane, Clare Gould, Kimberley Jones, David Hamm, Dipti Talaulikar, Jonathan Ellis, Frank Vari, Simone Birch, Erica Han, Peter Wood, Kim-Anh Le Cao, Michael R Green, Pauline Crooks, Sanjiv Jain, Joshua Tobin, Raymond J Steptoe, Maher K Gandhi
PURPOSE: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo Diffuse Large B-cell Lymphoma (DLBCL), and the TCR's impact on survival. EXPERIMENTAL DESIGN: We performed high-throughput unbiased TCRBeta sequencing on a population based cohort of 92 DLBCL patients treated with conventional (i.e. non-checkpoint blockade) frontline 'R-CHOP' therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString{trade mark, serif}...
September 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Thomas Schachtner, Maik Stein, Petra Reinke
The number of kidney transplant recipients (KTRs) after nonrenal solid organ transplantation (SOT) has increased to almost 5%. Knowledge on patient and allograft outcomes, infections, and alloreactivity, however, remains scarce. We studied 40 KTRs after nonrenal SOT. 720 primary KTRs and 119 repeat KTRs were used for comparison. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. Alloreactive and CMV-specific T-cells were measured by interferon-γ Elispot assay. Patient survival in KTRs after SOT, primary and repeat KTRs was comparable...
September 17, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Thomas Schachtner, Petra Reinke
BACKGROUND: Because of the strikingly increased risk of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-seronegative kidney transplant recipients (KTRs) from EBV-seropositive donors-EBV(D(+) R(-) ), special strategies need to be defined to prevent EBV transmission and EBV viremia. METHODS: We studied all KTRs at our center between 2008 and 2012. Seventeen of 402 KTRs (4.2%) were identified as EBV(D(+) R(-) ), among which 5 KTRs received kidneys from living donors and 12 KTRs from deceased donors...
September 15, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Ivan V Litvinov, Anna Shtreis, Kenneth Kobayashi, Steven Glassman, Matthew Tsang, Anders Woetmann, Denis Sasseville, Niels Ødum, Madeleine Duvic
Most skin malignancies are caused by external and often preventable environmental agents. Multiple reports demonstrated that cutaneous T-cell lymphomas (CTCL) can occur in married couples and cluster in families. Furthermore, recent studies document geographic clustering of this malignancy in Texas as well as in other areas of the United States. Multiple infectious, occupational, and medication causes have been proposed as triggers or promoters of this malignancy including hydrochlorothiazide diuretics, Staphylococcus aureus, dermatophytes, Mycobacterium leprae, Chlamydia pneumoniae, human T-Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV)...
July 2016: Oncoimmunology
Takanobu Tagawa, Manuel Albanese, Mickaël Bouvet, Andreas Moosmann, Josef Mautner, Vigo Heissmeyer, Christina Zielinski, Dominik Lutter, Jonathan Hoser, Maximilian Hastreiter, Mitch Hayes, Bill Sugden, Wolfgang Hammerschmidt
Epstein-Barr virus (EBV) is a tumor virus that establishes lifelong infection in most of humanity, despite eliciting strong and stable virus-specific immune responses. EBV encodes at least 44 miRNAs, most of them with unknown function. Here, we show that multiple EBV miRNAs modulate immune recognition of recently infected primary B cells, EBV's natural target cells. EBV miRNAs collectively and specifically suppress release of proinflammatory cytokines such as IL-12, repress differentiation of naive CD4(+) T cells to Th1 cells, interfere with peptide processing and presentation on HLA class II, and thus reduce activation of cytotoxic EBV-specific CD4(+) effector T cells and killing of infected B cells...
September 19, 2016: Journal of Experimental Medicine
Emily Milford, Caroline Winslow, Rebecca Danhof
Posttransplantation lymphoproliferative disorder (PTLD) is a rare complication of solid organ or allogenic bone marrow transplantation. Cases localized to the skin are even rarer, with only around 100 cases recorded in the literature [2]. We present a case of 60 year-old-woman, a lung transplant recipient, who presented with an asymptomatic violaceous nodule on her left medial calf. Histopathology was consistent with PTLD of the B-cell subtype, EBV negative. This case is unique in that it was of the B cell subtype of cutaneous PTLD, which has been less commonly observed than the T cell subtype...
2016: Dermatology Online Journal
Davey M Smith, Masato Nakazawa, Michael L Freeman, Christy M Anderson, Michelli F Oliveira, Susan J Little, Sara Gianella
BACKGROUND:  A low CD4/CD8 ratio in human immunodeficiency virus (HIV)-infected individuals is associated with inflammation and higher risk of non-AIDS morbidity and mortality. In this study, we investigated the effect of subclinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) replication on CD4(+) and CD8(+) T-cell dynamics when antiretroviral therapy (ART) is started during early infection. METHODS:  We investigated 604 peripheral blood mononuclear cell samples from 108 CMV- and EBV-seropositive HIV-infected men who have sex with men, who started ART within a median of 4 months from their estimated date of infection and were followed for a median of 29...
September 6, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
H Liu, X L Tang, J R Liu, H M Li, S Y Zhao
OBJECTIVE: To analyze clinical and genetic features of activated PI3K-δ syndrome (APDS), a new form of immunodeficiency disease caused by PIK3CD gene mutation. METHOD: Data of two patients diagnosed as APDS at Second Department of Respiratory Medicine of Beijing Children's Hospital Affiliated to Capital Medical University in 2015 were retrospectively reviewed. Pathogenetic genes were screened by whole exome sequencing, and identified by first generation sequencing...
September 2016: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Wook Youn Kim, Ho Young Jung, Soo Jeong Nam, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway blockade has emerged as a promising strategy for cancer therapy. Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive disease characterized by a strong association with Epstein-Barr virus (EBV), and chronic EBV infection is known to induce PD-L1 expression. However, the PD-1/PD-L1 pathway status in ENKTL remains elusive. Thus, the expression pattern of PD-1 and PD-L1 was investigated in 73 ENKTL cases, and its clinicopathological features and prognostic significance were analyzed...
September 5, 2016: Virchows Archiv: An International Journal of Pathology
Bao-Hua Yu, Ruo-Hong Shui, Wei-Qi Sheng, Chao-Fu Wang, Hong-Fen Lu, Xiao-Yan Zhou, Xiong-Zeng Zhu, Xiao-Qiu Li
PURPOSE: To investigate the clinicopathological features, survival and prognostic factors of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL). METHODS: Clinical and histological characteristics of PI-ENKTCL cases were retrospectively evaluated. Immunohistochemical phenotype and status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. The overall survival and prognostic parameters were also analyzed...
2016: PloS One
Yi Zhou, Marc K Rosenblum, Ahmet Dogan, Achim A Jungbluth, April Chiu
Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disorders may be seen in patients with angioimmunoblastic T cell lymphoma (AITL). Although both nodal and extranodal sites of involvement have been described, central nervous system involvement by B cell lymphoma following AITL has not previously been documented. We report a first example of such unusual presentation, in which an 80-year-old man developed diffuse large B cell lymphoma (DLBCL) in the cerebellum 4 months after the initial diagnosis of AITL...
December 2015: Journal of Hematopathology
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