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EBV T cells

Weili Wang, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C Knepper, Zhaoqian Liu, Wei Zhang, Howard L Mcleod, Yijing He
Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection. Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy...
February 23, 2018: Oncotarget
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Alessandro Antônio Costa Pereira, Christian Barros Ferreira, João Adolfo Costa Hanemann, Livia Maris Ribeiro Paranaiba, Patricia Peres Iucif Pereira, Carla Isabelly Rodrigues-Fernandes, Celeste Sánchez-Romero, Oslei Paes de Almeida, Felipe Paiva Fonseca
Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder driven by Esptein-Barr virus (EBV) that most commonly affects the lungs, although extra pulmonary sites like the central nervous system, skin, liver and kidney can also be involved. It is microscopically characterized by an angiocentric and angiodestructive growth pattern, predominantly composed by small T-cells, although a smaller population of atypical large B-cells is considered the true neoplastic component. Oral cavity involvement of LYG has rarely been described and the diagnosis of this neoplasm is very difficult...
March 14, 2018: Head and Neck Pathology
Hiroyuki Abe, Ruri Saito, Takashi Ichimura, Akiko Iwasaki, Sho Yamazawa, Aya Shinozaki-Ushiku, Teppei Morikawa, Tetsuo Ushiku, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0...
March 13, 2018: Virchows Archiv: An International Journal of Pathology
Franklin R Toapanta, Paula J Bernal, Karen L Kotloff, Myron M Levine, Marcelo B Sztein
BACKGROUND: Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role...
March 13, 2018: Journal of Translational Medicine
X L Shi, J L Xie, X G Zhou
Objective: To evaluate the clinicopathological features, diagnosis and management of primary testicular NK/T cell lymphoma (NKTCL). Methods: Six cases of primary testicular NKTCL at Beijing Friendship Hospital, Capital Medical University from January 2007 to December 2016 were retrospectively analyzed for the morphology, immunephenotype and outcome, and relevant literature was reviewed. Results: The median age of patients at diagnosis was 45 years(range 32-65 years). All patients presented with testicular masses as initial symptoms (6/6), five cases (5/6) were on the right...
March 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Li Liu, Xuyan Zhang, Sizhou Feng
Epstein-Barr virus related post-transplant lymphoproliferative disorders (EBV-PTLDs) are rare but potentially fatal complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by uncontrolled proliferation of EBV-infected lymphocytes. The most frequent risk factors include T cell depletion of graft, HLA mismatch, severe graft versus host disease (GVHD), EBV sero-mismatch (recipient-/donor+) and so on. EBV-PTLDs commonly manifest as fever and lymphadenopathy and may rapidly progress to multi-organ failure and even death...
March 9, 2018: Biology of Blood and Marrow Transplantation
Elisenda Alari-Pahissa, Antía Moreira, Ana Zabalza, Roberto Alvarez-Lafuente, Elvira Munteis, Andrea Vera, Rafael Arroyo, Jose C Alvarez-Cermeño, Luisa Maria Villar, Miguel López-Botet, Jose E Martínez-Rodríguez
BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has been recently associated with a lower multiple sclerosis (MS) susceptibility, remaining controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in early MS as compared to non-early MS patients, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses...
March 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Alessia Gallo, Monica Miele, Ester Badami, Pier Giulio Conaldi
Patients following solid organ transplantation show a higher risk of developing cancer compared to the general population. Elevated risk is likely due to the interplay of a combination of factors, such as chronic inflammation, coexisting medical conditions, immunosuppressive regimen and persistent infection with oncogenic viruses. In addition, the tumor microenvironment plays a pivotal role in cancer progression, by driving recruitment and in situ differentiation of anti-inflammatory cells of the adaptive and innate immune system such as regulatory T cells, Th17, Dendritic Cells, Myeloid Derived Suppressor Cells, Type 2 Macrophages...
February 16, 2018: Cellular Immunology
Jun-Ichi Kawada, Shotaro Ando, Yuka Torii, Takahiro Watanabe, Yoshitaka Sato, Yoshinori Ito, Hiroshi Kimura
Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in EBV-associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV-associated lymphoma cell lines...
March 9, 2018: Cancer Medicine
Qian Fei, Xiao-Kang Tian, Jing Wu, Hong-Ming Zhu, Yan Wang, Fan-Yu Peng, Wen-Jun Zhang, Li Yin, Xia He
Extranodal NK/T-cell lymphoma is closely associated with Epstein-Barr virus (EBV) infection. However, the prognostic value of EBV-DNA in extranodal NK/T-cell lymphoma remains unclear. Thus, we conducted a meta-analysis to estimate its prognostic significance. PubMed, EMBASE, and Web of Science were used to search for studies conducted until June 12, 2017. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated to evaluate the prognostic value of pretreatment EBV-DNA on the overall survival of extranodal NK/T-cell lymphoma...
2018: OncoTargets and Therapy
Stefan D Dojcinov, Falko Fend, Leticia Quintanilla-Martinez
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification...
March 7, 2018: Pathogens
Dai Yu-Mei, Hai-Ying Liu, Yun-Feng Liu, Yuan Zhang, Wei He
The engagement of Epstein-Barr virus (EBV)-induced protein ligands in γδ T cell-mediated anti-EBV immunity especially in EBV associated B cell malignancies has not been fully elucidated. Previously we reported the overexpression of human MutS homologue 2(hMSH2), a stress inducible protein ligand for human γδ T cells, on EBV-transformed B lymphoblastic cell lines (B-LCLs). In this study, we first generated EBV-transformed B-LCLs from peripheral blood mononuclear cells (PBMCs) of healthy volunteers with B95-8 cellular supernatant and cyclosporine A...
March 7, 2018: Immunology
Bhushan Dharmadhikari, Emily Nickles, Zulkarnain Harfuddin, Nur Diana Binte Ishak, Qun Zeng, Antonio Bertoletti, Herbert Schwarz
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs...
March 5, 2018: Cancer Immunology, Immunotherapy: CII
Jianan Zhou, Canjing Zhang, Xianxian Sui, Shengxuan Cao, Feng Tang, Shuhui Sun, Songmei Wang, Bobin Chen
We investigated the anti-tumour effects and the underlying molecular mechanisms of a new oral histone deacetylase inhibitor (HDACi), chidamide, in NK/T cell lymphoma (NKTCL), a rare and highly aggressive non-Hodgkin lymphoma with poor outcomes. SNT-8 and SNK-10 NKTCL cell lines were exposed to different concentrations of chidamide for the indicated time. The treated cells were analysed for cell proliferation, cell cycle progression, and cell apoptosis. Proteins in the AKT/mTOR and MAPK signalling pathways and the DNA damage response (DDR) cell cycle checkpoint pathway were measured by Western blotting...
March 5, 2018: Investigational New Drugs
Kyosuke Kanai, Ah-Mee Park, Akiko Watanabe, Tomohiro Arikawa, Teruhito Yasui, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
IL-27 is an immunoregulatory cytokine consisting of p28 and EBI3. Its receptor also has two subunits, WSX1 and gp130. Although IL-27 promotes Th1 differentiation in naive T cells, it also induces IL-10 expression in effector Th1 cells to curtail excessive immune responses. By using p28-deficient mice and WSX1-deficient mice (collectively called IL-27-deficient mice), we examined the role of IL-27 in primary infection by murine γ-herpesvirus 68 (MHV68), a murine model of EBV. Upon airway infection with MHV68, IL-27-deficient mice had more aggravated lung inflammation than wild-type mice, although MHV68 infection per se was better controlled in IL-27-deficient mice...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Neha Mehta-Shah, Nancy L Bartlett
Addition of brentuximab vedotin, a CD30 targeted antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab, to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine, may result in prolonged survivals with minimal or modest effect on quality of life...
March 2, 2018: Blood
Jeong Hoo Lee, Jahyang Choi, Yong-Oon Ahn, Tae Min Kim, Dae Seog Heo
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant disease that is associated with Epstein-Barr viral (EBV) infection. To date, the mechanism of viral entry into NK cells remains uncertain. Here, we investigated this mechanism using human NK cells in vitro. CD21 mRNA expression, an EBV-entry receptor, was transiently detected in NK cells after exosome treatment, and levels decreased after further culture. CD21 protein expression was also transiently transferred to NK cells after co-culture with an EBV-positive Burkitt lymphoma cell line (Raji) via trogocytosis...
January 17, 2018: Cellular Immunology
Anette Holck Draborg, Niclas Stefan Rasmussen, Janni Lisander Larsen, Charlotte Sværke Jørgensen, Noreen Sandhu, Kristin Skogstrand, Søren Jacobsen, Gunnar Houen
We investigated immune responses to a lytic cytomegalovirus antigen (CMVpp52), and to a lytic human herpes virus (HHV) 6 antigen (HHV6p41), in systemic lupus erythematosus (SLE) patients and healthy controls (HCs), in order to clarify if the previously established impaired responses to Epstein-Barr virus (EBV) in SLE patients is a general defect in their responses against (all) HHVs. Multiplex Luminex technology results showed a normal induction of five quantified cytokines (interferon γ, interleukin(IL)12, IL17, IL10, and tumor necrosis factor α) in SLE patients compared to HCs upon stimulation with CMVpp52 and HHV6p41...
2018: PloS One
Toshiaki Ono, Yuriko Fujita, Tetsuro Matano, Satoshi Takahashi, Tomohiro Morio, Ai Kawana-Tachikawa
Adoptive transfer of virus-specific T cells has emerged as a promising therapeutic approach for treatment of virus infections in immunocompromised hosts. Characterization of virus-specific T cells provides essential information for the curative mechanism of the treatment. In this study, we developed a T cell epitope mapping system for 718 overlapping peptides spanning 6 viral proteins from three viruses (pp65 and IE1 from CMV; LMP1, EBNA1 and BZLF1 from EBV; Penton from AdV). PBMCs from 33 healthy Japanese donors were stimulated with these peptides and virus-specific CD4+ and CD8+ T cell were expanded in vitro in the presence of IL4 and IL7...
February 28, 2018: Japanese Journal of Infectious Diseases
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