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https://www.readbyqxmd.com/read/27895177/ox40-cooperates-with-icos-to-amplify-follicular-th-cell-development-and-germinal-center-reactions-during-infection
#1
Vikas Tahiliani, Tarun E Hutchinson, Georges Abboud, Michael Croft, Shahram Salek-Ardakani
Cognate interactions between T follicular helper (Tfh) cells and B cells are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. In this study, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral Ags...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27878248/immunomodulatory-effects-of-ox40ig-gene-modified-adipose-tissue-derived-mesenchymal-stem-cells-on-rat-kidney-transplantation
#2
Tao Liu, Yue Zhang, Zhongyang Shen, Xunfeng Zou, Xiaobo Chen, Li Chen, Yuliang Wang
Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immunosuppressive activity in preventing renal allograft rejection...
November 21, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#3
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856634/fc-engineering-approaches-to-enhance-the-agonism-and-effector-functions-of-an-anti-ox40-antibody
#4
Di Zhang, Monica V Goldberg, Mark L Chiu
Agonistic antibodies directed against immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising cancer immunotherapies. Several Fc engineering approaches were discovered recently that can augment the anti-tumor activities of TNFR antibodies by enhancing their agonistic activities and/or effector functions. In this study, we evaluated and compared these approaches for their effects on an anti-OX40 antibody. Both S267E/L328F and V12 mutations of an anti-OX40 antibody can facilitate enhanced binding to FcγRIIB and result in increased FcγRIIB crosslinking mediated agonist activity...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27843539/regulatory-and-activated-effector-t-cells-in-chronic-hepatitis-c-virus-relation-to-autoimmunity
#5
Hanan Fouad, Maissa El Raziky, Eman Medhat Hassan, Ghada Mahmoud Abdel Aziz, Samar K Darweesh, Ahmed Reda Sayed
AIM: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS: A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group...
October 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#6
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27826331/the-roles-of-cd137-signaling-in-atherosclerosis
#7
REVIEW
In-Hyuk Jung, Goo Taeg Oh
The tumor necrosis factor receptor superfamily (TNFRSF), which includes CD40, LIGHT, and OX40, plays important roles in the initiation and progression of cardiovascular diseases, involving atherosclerosis. CD137, a member of TNFRSF, is a well-known activation-induced T cell co-stimulatory molecule and has been reported to be expressed in human atherosclerotic plaque lesions, and plays pivotal roles in mediating disease processes. In this review, we focus on and summarize recent advances in mouse studies on the involvement of CD137 signaling in the pathogenesis and plaque stability of atherosclerosis, thereby highlighting a valuable therapeutic target in atherosclerosis...
November 2016: Korean Circulation Journal
https://www.readbyqxmd.com/read/27825407/aberrant-expressions-of-immune-factors-facilitate-the-disequilibrium-of-br-immune-status-in-cervical-cancer
#8
Min-Yi Zhao, Juan Zhao, Ting Yang, Li Wang, Mei-Li Pei, Si-Juan Tian, Yang Yu, Xiao-Feng Yang
Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR)...
October 10, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/27753891/ish-nia-os-06-putative-mechanisms-for-cerebrovascular-remodelling-in-the-spontaneously-hypertensive-rat-shr-using-transcriptomics
#9
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27703035/cd4-t-cells-co-expressing-cd134-ox40-harbor-significantly-increased-levels-of-hhv-6b-dna-following-umbilical-cord-blood-transplantation
#10
Joshua C Pritchett, Jaime S Green, Angela M Thomm, Konstance K Knox, Michael R Verneris, Troy C Lund
Human herpesvirus-6B (HHV-6B) commonly reactivates after umbilical cord blood transplant (UCBT) and is associated with delayed engraftment, fever, rash, and CNS dysfunction. Recently CD134 (OX40) has been implicated as a potential viral entry receptor. We evaluated CD4(+)CD134(+)/(neg-lo) and CD8(+) CD134(+)/(neg-lo) cells at day +28 after UCBT in 20 subjects with previously documented HHV-6 reactivation and persistent viremia. Analysis of CD4(+)CD134(+) cells compared to CD4(+)CD134(neg-lo) cells showed 0...
October 4, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27643237/ish-nia-os-06-putative-mechanisms-for-cerebrovascular-remodelling-in-the-spontaneously-hypertensive-rat-shr-using-transcriptomics
#11
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27622025/regulatory-t-cells-with-multiple-suppressive-and-potentially-pro-tumor-activities-accumulate-in-human-colorectal-cancer
#12
Eleonora Timperi, Ilenia Pacella, Valeria Schinzari, Chiara Focaccetti, Luca Sacco, Francesco Farelli, Roberto Caronna, Gabriella Del Bene, Flavia Longo, Antonio Ciardi, Sergio Morelli, Anna Rita Vestri, Piero Chirletti, Vincenzo Barnaba, Silvia Piconese
Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27622011/combined-treatment-with-dabrafenib-and-trametinib-with-immune-stimulating-antibodies-for-braf-mutant-melanoma
#13
Blanca Homet Moreno, Stephen Mok, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Antoni Ribas
The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAF (V600E) mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compared with single therapy alone groups support the idea that combining dabrafenib, trametinib and immunotherapy based on PD-1 blockade could be an interesting approach in the treatment of metastatic melanoma...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27608046/t-regulatory-cells-and-vaccination-pay-attention-and-do-not-neglect-them-lessons-from-hiv-and-cancer-vaccine-trials
#14
REVIEW
Vedran Brezar, Véronique Godot, Liang Cheng, Lishan Su, Yves Lévy, Nabila Seddiki
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit...
September 5, 2016: Vaccines
https://www.readbyqxmd.com/read/27590513/activation-and-selective-il-17-response-of-human-v%C3%AE-9v%C3%AE-2-t-lymphocytes-by-tlr-activated-plasmacytoid-dendritic-cells
#15
Elena Lo Presti, Nadia Caccamo, Valentina Orlando, Francesco Dieli, Serena Meraviglia
Vγ9Vδ2 T cells and plasmacytoid dendritic cells (pDCs) are two distinct cell types of innate immunity that participate in early phases of immune response. We investigated whether a close functional relationship exists between these two cell populations using an in vitro co-culture in a human system.pDCs that had been activated by IL-3 and the TLR9 ligand CpG induced substantial activation of Vγ9Vδ2 T cells upon co-culture, which was cell-to-cell contact dependent, as demonstrated in transwell experiments, but that did not involve any of the costimulatory molecules potentially expressed by pDCs or Vγ9V2 T cells, such as ICOS-L, OX40 and CD40L...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27580926/ox40-regulates-pressure-overload-induced-cardiac-hypertrophy-and-remodelling-via-cd4-t-cells
#16
Qing-Qing Wu, Yuan Yuan, Xiao-Han Jiang, Yang Xiao, Zheng Yang, Zhen-Guo Ma, Hai-Han Liao, Yuan Liu, Wei Chang, Zhou-Yan Bian, Qi-Zhu Tang
OX40, which belongs to the tumour necrosis factor (TNF)-receptor family, is a costimulatory receptor that can potentiate T-cell receptor signalling on the surface of T-lymphocytes. The role of OX40 in non-immune systems, particularly the cardiovascular system, has not been defined. In the present study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In the present study, cardiac hypertrophy was induced by aortic banding (AB) in OX40 knockout (KO) mice and wild-type (WT) mice...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27549124/reduction-of-mdscs-with-all-trans-retinoic-acid-improves-car-therapy-efficacy-for-sarcomas
#17
Adrienne H Long, Steven L Highfill, Yongzhi Cui, Jillian P Smith, Alec J Walker, Sneha Ramakrishna, Rana El-Etriby, Susana Galli, Maria G Tsokos, Rimas J Orentas, Crystal L Mackall
Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2...
October 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27533501/immunotherapy-in-kidney-cancer-the-past-present-and-future
#18
Hans Hammers
PURPOSE OF REVIEW: Kidney cancer, in particular clear cell renal cell carcinoma (ccRCC) has long been considered to be sensitive to immunotherapies. With the recent breakthroughs in immunotherapy for solid tumors and the recent approval of the first immune checkpoint inhibitor for ccRCC, we are reviewing the history of immunotherapy in kidney cancer, describing its current state and look into the future of a rapidly evolving landscape in immunotherapy for kidney cancer. RECENT FINDINGS: Systemic treatment options over the past decade have been dominated by targeted therapies inhibiting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27503208/immunotherapy-expands-and-maintains-the-function-of-high-affinity-tumor-infiltrating-cd8-t-cells-in-situ
#19
Amy E Moran, Fanny Polesso, Andrew D Weinberg
Cancer cells harbor high-affinity tumor-associated Ags capable of eliciting potent antitumor T cell responses, yet detecting these polyclonal T cells is challenging. Therefore, surrogate markers of T cell activation such as CD69, CD44, and programmed death-1 (PD-1) have been used. We report in this study that in mice, expression of activation markers including PD-1 is insufficient in the tumor microenvironment to identify tumor Ag-specific T cells. Using the Nur77GFP T cell affinity reporter mouse, we highlight that PD-1 expression can be induced independent of TCR ligation within the tumor...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27479233/chimeric-antigen-receptor-car-t-cell-therapy-targeting-cd19-positive-leukemia-and-lymphoma-in-the-context-of-stem-cell-transplantation
#20
Maria-Luisa Schubert, Angela Gabriele Hückelhoven, Jean-Marc Hoffmann, Anita Schmitt, Patrick Wuchter, Leopold Sellner, Susanne Hofmann, Anthony D Ho, Peter Dreger, Michael Schmitt
Novel therapies with chimeric antigen receptor (CAR) transduced T cells (TCs) sparked new hope for patients with relapsed or refractory CD19-positive leukemia or lymphoma even after stem cell therapies. This review focuses on CARs recognizing the B cell antigen CD19. Both retro- and lentiviral vectors are used encoding the different anti-CD19 CAR constructs comprising costimulatory molecules like CD28, CD137/4-1BB and OX40 either alone (2nd generation CARs) or in combination (3rd generation CARs). Current up-to-date published studies on anti-CD19 CAR therapy for acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and Non-Hodgkin lymphoma (NHL) with observed side effects are discussed and an outlook on 59 ongoing trials is given...
August 1, 2016: Human Gene Therapy
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