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https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#1
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#2
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28289860/the-pd-l1-pd-1-pathway-promotes-dysfunction-but-not-exhaustion-in-tumor-responding-t-cells-from-pleural-effusions-in-lung-cancer-patients
#3
Heriberto Prado-Garcia, Susana Romero-Garcia, Alejandra Puerto-Aquino, Uriel Rumbo-Nava
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts...
March 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28288971/activation-of-cd137-signaling-promotes-angiogenesis-in-atherosclerosis-via-modulating-endothelial-smad1-5-nfatc1-pathway
#4
Jiayi Weng, Cuiping Wang, Wei Zhong, Bo Li, Zhongqun Wang, Chen Shao, Yao Chen, Jinchuan Yan
BACKGROUND: Excessive angiogenesis is a key feature of vulnerable atherosclerotic plaques, and is considered an independent predictor of cardiovascular risk. CD137 signaling has previously been shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulating angiogenesis has not been reported. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE(-/-)) mice were used as the in vivo model of atherosclerosis. Masson and immunohistochemical analysis of atherosclerotic plaques and Matrigel plug assay were used to evaluate the angiogenesis...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28284008/effective-and-persistent-antitumor-activity-of-her2-directed-car-t-cells-against-gastric-cancer-cells-in-vitro-and-xenotransplanted-tumors-in-vivo
#5
Yanjing Song, Chuan Tong, Yao Wang, Yunhe Gao, Hanren Dai, Yelei Guo, Xudong Zhao, Yi Wang, Zizheng Wang, Weidong Han, Lin Chen
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties...
March 10, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28280290/amelioration-of-inflammatory-cytokines-mix-stimulation-a-pretreatment-of-cd137-signaling-study-on-vsmc
#6
Wei Zhong, Bo Li, Xiao Yang Li, Zhong Qun Wang, Chen Shao, Cui Ping Wang, Rui Chen, Jin Chuan Yan
Previous studies showed little CD137 expressed in normal vascular smooth muscle cells (VSMCs) and it is important to find a valid way to elevate it before studying its function. The level of CD137 was detected by RT-PCR, western blot, and flow cytometry, respectively. CD137 signaling activation was activated by agonist antibody and measured through phenotype transformation indicators and cell functions. Proteins in supernatants were detected by ELISA. The total CD137 elevates under different concentrations of CM treatment...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28274286/galectins-expressed-differently-in-genetically-susceptible-c57bl-6-and-resistant-balb-c-mice-during-acute-ocular-toxoplasma-gondii-infection
#7
S-J Chen, Y-X Zhang, S-G Huang, F-L Lu
Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection...
March 9, 2017: Parasitology
https://www.readbyqxmd.com/read/28238741/microparticles-in-nasal-lavage-fluids-in-chronic-rhinosinusitis-potential-biomarkers-for-diagnosis-of-aspirin-exacerbated-respiratory-disease
#8
Toru Takahashi, Atsushi Kato, Sergejs Berdnikovs, Whitney W Stevens, Lydia A Suh, James Norton, Roderick G Carter, Kathleen E Harris, Anju T Peters, Kathryn E Hulse, Leslie C Grammer, Kevin Welch, Stephanie Shintani-Smith, Bruce K Tan, David B Conley, Robert C Kern, Bruce S Bochner, Robert P Schleimer
BACKGROUND: Microparticles (MPs) are submicron sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been utilized as biomarkers to evaluate cell injury or activation in patients with pathological conditions. OBJECTIVE: To compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with NP (CRSwNP) and aspirin exacerbated respiratory disease (AERD)...
February 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#9
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28218958/cd137-is-a-useful-marker-for-identifying-cd4-t-cell-responses-to-mycobacterium-tuberculosis
#10
Zhuo-Hong Yan, Xiao-Fang Zheng, Ling Yi, Jing Wang, Xiao-Jue Wang, Pan-Jian Wei, Hong-Yan Jia, Li-Jun Zhou, Yan-Lin Zhao, Hong-Tao Zhang
Upregulation of CD137 on recently activated CD8(+) T cells has been used to identify rare viral and tumor antigen-specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD137 for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4(+) T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD137(+) CD4(+) T cells. We initially enrolled 31 active tuberculosis (TB) patients, 31 individuals with latent TB infection (LTBI), and 25 healthy donors...
February 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28154348/promoting-effect-of-%C3%AE-tocopherol-on-beige-adipocyte-differentiation-in-3t3-l1-cells-and-rat-white-adipose-tissue
#11
Rieko Tanaka-Yachi, Chie Takahashi-Muto, Kazuya Adachi, Yukina Tanimura, Yoshinori Aoki, Taisuke Koike, Chikako Kiyose
Thermogenic adipocytes that are distinct from classical brown adipocytes (beige adipocytes) were identified in 2012. Beige adipocytes are also called inducible brown adipocytes because their differentiation is induced by a number of physiological stimuli, including adrenaline or myokines. PPARγ is the master regulator of adipogenesis and promotes thermogenic adipocyte differentiation. A PPARγ agonist also promotes thermogenic adipocyte differentiation in mouse white adipose tissues. The vitamin E analog α-tocopherol promotes PPARγ expression and induces mRNA expression of target genes...
2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-immunotherapy-strategies-enhancing-effector-nk-cells
#12
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only natural killer (NK) cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28100346/-impact-of-cd137-cd137l-signaling-mediated-exocytosis-of-autophagosome-within-vascular-smooth-muscle-cells-on-the-formation-of-atherosclerotic-calcification
#13
B Li, X Y Li, W Zhong, C Shao, Z Q Wang, W Yuan, J C Yan
Objective: To explore whether CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells (VSMCs) could influence the formation of atherosclerotic calcification. Methods: Fifteen 8-week-old male ApoE(-/-)(C57BL/6J-KO) mice fed with high fat diet for 5 weeks were randomly divided into three groups by using stochastic indicator method as follows: control group, n=5; agonist-CD137 group: agonist-CD137 antibody 200 μg/2 weeks for 4 weeks, ip, n=5; anti-CD137 group: 200 μg anti-CD137 antibody+ 200 μg agonist-CD137 antibody/2 weeks for 4 weeks, ip, n=5...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28063668/activation-of-cd137-signaling-accelerates-vascular-calcification-in-vivo-and-vitro
#14
Yao Chen, Abdul Basit Bangash, Juan Song, Wei Zhong, Cuiping Wang, Chen Shao, Zhongqun Wang, Jinchuan Yan
OBJECTIVES: Vascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular risk. CD137 signaling has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In the present study, we investigated the effect of CD137 signaling on vascular calcification in ApoE(-/-) mice and in vascular smooth muscle cells (VSMCs) of mice...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28056236/-cd137-cd137l-signaling-promotes-angiogenesis-in-atherosclerosis-plaque-of-mice-through-activating-nuclear-factor-of-activated-t-cells-c1
#15
J Y Weng, J C Yan, Y Chen, Z Q Wang, C P Wang, C Shao
Objective: To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1 (NFATc1). Methods: Apolipoprotein E knock out mice were divided into the following groups: control group (n=5), CD137 activated group(n=5)and CD137 inhibited group (n=5). Immunohistochemistry was performed to detect the expression of CD31 in aortic plaque. Endothelial cells (bEnd.3) were purchased from ATCC and divided into the following groups: control group, IgG isotype control group, CD137 activated group and CD137 inhibited group...
December 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28018351/allorecognition-of-hla-c-mismatches-by-cd8-t-cells-in-hematopoietic-stem-cell-transplantation-is-a-complex-interplay-between-mismatched-peptide-binding-region-residues-hla-c-expression-and-hla-dpb1-disparities
#16
Florence Bettens, Stéphane Buhler, Jean-Marie Tiercy
HLA-C locus mismatches (MMs) are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT) and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C MMs, we have developed a one-way in vitro mixed lymphocyte reaction (MLR) assay allowing to quantify activated CD56(-)CD137(+)CD8(+) lymphocytes in HLA-C incompatible combinations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011265/involvement-of-ly6c-4-1bb-and-klrg1-in-the-activation-of-lamina-propria-lymphocytes-in-the-small-intestine-of-sanroque-mice
#17
Dina Montufar-Solis, Alexander Williams, Nadarajah Vigneswaran, John R Klein
Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquin(san/san) or sanroque mice, develop broad-spectrum chronic inflammatory conditions and autoimmune pathologies. Our laboratory recently reported that sanroque mice also develop extensive inflammation that is localized in the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28000531/cytokines-and-metabolic-factors-regulate-tumoricidal-t-cell-function-during-cancer-immunotherapy
#18
Adam J Adler, Payal Mittal, Joseph M Ryan, Beiyan Zhou, Jeffrey S Wasser, Anthony T Vella
Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27979383/atezolizumab-versus-docetaxel-in-patients-with-previously-treated-non-small-cell-lung-cancer-oak-a-phase-3-open-label-multicentre-randomised-controlled-trial
#19
Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara
BACKGROUND: Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer. METHODS: We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1...
January 21, 2017: Lancet
https://www.readbyqxmd.com/read/27942918/immunological-low-dose-radiation-modulates-the-pediatric-medulloblastoma-antigens-and-enhances-antibody-dependent-cellular-cytotoxicity
#20
Arabinda Das, Daniel McDonald, Stephen Lowe, Amy-Lee Bredlau, Kenneth Vanek, Sunil J Patel, Samuel Cheshier, Ramin Eskandari
BACKGROUND: Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341)...
December 9, 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
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