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https://www.readbyqxmd.com/read/28651374/cd70-a-novel-target-of-car-t-cell-therapy-for-gliomas
#1
Linchun Jin, Haitao Ge, Yu Long, Changlin Yang, Yifan Emily Chang, Luyan Mu, Elias J Sayour, Gabriel De Leon, Qiong J Wang, James C Yang, Paul S Kubilis, Hongbo Bao, Songsong Xia, Dunyue Lu, Yingjun Kong, Li Hu, Yujiao Shang, Chencheng Jiang, Jing Nie, Shimin Li, Yunhe Gu, Jiahang Sun, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Cancer immunotherapy represents a promising treatment approach for malignant-gliomas, but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified CD70 as a novel immunosuppressive ligand and glioma target. Methods: Normal tissues derived from 52 different organs, and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression...
June 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28650673/evidence-of-interleukin-21-reduction-in-osteosarcoma-patients-due-to-pd-1-pd-l1-mediated-suppression-of-follicular-helper-t-cell-functionality
#2
Wenwu Gao, Junjie Zhou, Bin Ji
Interleukin 21 (IL-21) is crucial for the development of a robust CD8(+) T cell response and has been shown to promote antitumor immunity. Despite the fact that osteosarcoma presents significant genetic instability with a high immunogenic potential, the antitumor immune response in osteosarcoma is ineffective. We investigated whether this was due to impaired IL-21 responses. We found that the circulating CD4(+) T cells, a major source of IL-21, had reduced capacity to express IL-21 in osteosarcoma patients compared to healthy controls...
June 26, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28650437/antigen-capturing-nanoparticles-improve-the-abscopal-effect-and-cancer-immunotherapy
#3
Yuanzeng Min, Kyle C Roche, Shaomin Tian, Michael J Eblan, Karen P McKinnon, Joseph M Caster, Shengjie Chai, Laura E Herring, Longzhen Zhang, Tian Zhang, Joseph M DeSimone, Joel E Tepper, Benjamin G Vincent, Jonathan S Serody, Andrew Z Wang
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties...
June 26, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#4
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649247/an-antigen-presenting-and-apoptosis-inducing-polymer-microparticle-prolongs-alloskin-graft-survival-by-selectively-and-markedly-depleting-alloreactive-cd8-t-cells
#5
Wei Wang, Khawar Ali Shahzad, Miaochen Li, Aifeng Zhang, Lei Zhang, Tao Xu, Xin Wan, Chuanlai Shen
Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs) has been developed by co-coupling peptide-major histocompatibility complex (pMHC) multimer and anti-Fas monoclonal antibody (mAb) onto the polymeric microparticles (MPs) to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649242/an-approach-for-a-synthetic-ctl-vaccine-design-against-zika-flavivirus-using-class-i-and-class-ii-epitopes-identified-by-computer-modeling
#6
Edecio Cunha-Neto, Daniela S Rosa, Paul E Harris, Tim Olson, Alex Morrow, Serban Ciotlos, Charles V Herst, Reid Martin Rubsamen
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648946/end-of-therapy-minimal-residual-disease-mrd-measurement-in-children-with-all-does-not-predict-relapse
#7
Tahani Hani Sarrawi, Ismael Zayyat, Fareed Barakat, Maha Rezeq, Salam Abu Jmaian, Faris Madanat
Minimal residual disease (MRD) monitoring opened a new era for childhood acute lymphoblastic leukemia (ALL), and is widely used for risk adapted therapy in the major study groups (Borowitz et al. 2015; Eckert et al., 2015; Peregud-Pogorzelsk et al., 2003). MRD is measured either by polymerase chain reaction (PCR) or flow cytometry (FCM) (Campana, 2009). Most studies have concentrated on measuring MRD during or at end of induction, and after consolidation therapy, to stratify patients and to predict relapse (Sutton et al...
June 17, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#8
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648760/corneal-endothelial-cells-activate-innate-and-acquired-arm-of-anti-viral-responses-after-cytomegalovirus-infection
#9
Dai Miyazaki, Ryu Uotani, Michiko Inoue, Tomoko Haruki, Yumiko Shimizu, Keiko Yakura, Satoru Yamagami, Tatsuo Suzutani, Mayumi Hosogai, Hiroki Isomura, Yoshitsugu Inoue
Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined. To understand the immunopathology of endotheliitis, we examined how corneal endothelial cells prime the anti-viral immunity after CMV infection based on global transcriptional responses. To accomplish this, human corneal endothelial (HCEn) cells were infected with CMV, and the global transcriptional responses were determined by microarray analyses for primary anti-viral responses using network analysis...
June 22, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28648661/de-novo-epigenetic-programs-inhibit-pd-1-blockade-mediated-t-cell-rejuvenation
#10
Hazem E Ghoneim, Yiping Fan, Ardiana Moustaki, Hossam A Abdelsamed, Pradyot Dash, Pranay Dogra, Robert Carter, Walid Awad, Geoff Neale, Paul G Thomas, Ben Youngblood
Immune-checkpoint-blockade (ICB)-mediated rejuvenation of exhausted T cells has emerged as a promising approach for treating various cancers and chronic infections. However, T cells that become fully exhausted during prolonged antigen exposure remain refractory to ICB-mediated rejuvenation. We report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. Whole-genome bisulfite sequencing of antigen-specific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progressively acquired heritable de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade treatment...
June 21, 2017: Cell
https://www.readbyqxmd.com/read/28648519/an-upregulation-of-cd8-cd25-foxp3-t-cells-with-suppressive-function-through-interleukin-2-pathway-in-pulmonary-arterial-hypertension
#11
Rong Zhu, Liang Chen, Yaqiong Xiong, Nana Wang, Xiaochen Xie, Yongqing Hong, Zili Meng
Accumulating evidence suggests that abnormal inflammation plays a critical role in the pathogenesis of pulmonary arterial hypertension (PAH). CD8(+)CD25(+)Foxp3(+) T cell is a novel cell subtype, and its role in PAH is not yet investigated. Here, we observed that PAH patients presented a significant upregulation of CD8(+)CD25(+)Foxp3(+) T cells and a downregulation of CD4(+)CD25(+)Foxp3(+) T cells compared to healthy controls. Regardless, the total number of CD25(+)Foxp3(+) T cells in PAH patients was still smaller than that in healthy controls...
June 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28647888/osteoimmunology-in-bone-fracture-healing
#12
REVIEW
Takehito Ono, Hiroshi Takayanagi
PURPOSE OF REVIEW: In the process of bone fracture healing, inflammation is thought to be an essential process that precedes bone formation and remodeling. We review recent studies on bone fracture healing from an osteoimmunological point of view. RECENT FINDINGS: Based on previous observations that many types of immune cells infiltrate into the bone injury site and release a variety of molecules, recent studies have addressed the roles of specific immune cell subsets...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647026/s100b-correlation-with-active-vitiligo%C3%A2-depigmentation
#13
Stanca A Birlea
Vitiligo, the most common depigmenting disorder, is caused by immune destruction of melanocytes by cytotoxic CD8(+) T cells. One weakness in vitiligo management is the lack of an assessment method for active depigmentation. Beginning with reports about increased S100B levels in different inflammatory and tissue damage processes, Speeckaert et al. explored correlations between the S100B dynamics and vitiligo activity, identifying high circulating S100B levels in patients with active depigmentation which were strongly correlated with the extent of affected skin surface...
July 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646891/absence-of-batf3-results-in-reduced-liver-pathology-in-mice-infected-with-schistosoma-japonicum
#14
Lin Chen, Donghui Zhang, Wenyue Zhang, Yuxiao Zhu, Min Hou, Bingya Yang, Zhipeng Xu, Minjun Ji, Guanling Wu
BACKGROUND: The involvement of CD8(+)T cells in schistosomiasis is being increasingly appreciated, but the underlying mechanism is not well defined. RESULTS: In this study, we showed that the absence of Batf3 alleviated liver damage in Batf3 (-/-) mice infected with S. japonicum. We found alleviated liver granulomatous inflammation in Batf3 (-/-) mice with schistosomiasis japonica could not be attributed to the difference in schistosome egg or worm burden. The stronger Tc1 cell responses observed in Batf3 (-/-) mice suggested that the deletion of Batf3 resulted in more activation of CD8(+)T cells unexpectedly during the natural infection of schistosomes...
June 24, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#15
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646487/immunotoxic-effects-of-thymus-in-mice-following-exposure-to-nanoparticulate-tio2
#16
Fashui Hong, Yaoming Zhou, Yingjun Zhou, Ling Wang
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg(-1) body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices...
June 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28646160/loss-of-g%C3%AE-i-proteins-impairs-thymocyte-development-disrupts-t-cell-trafficking-and-leads-to-an-expanded-population-of-splenic-cd4-pd-1-cxcr5-t-cells
#17
Il-Young Hwang, Kathleen Harrison, Chung Park, John H Kehrl
Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in thymocyte and T cell function, we developed several mouse models. Gαi2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#18
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#19
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645781/immunomodulatory-mechanism-of-bushen-huoxue-recipe-alleviates-cyclophosphamide-induced-diminished-ovarian-reserve-in-mouse-model
#20
Cong Huang, Kunkun Song, Wenwen Ma, Jiahui Ding, Zhuo Chen, Mingmin Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice. MATERIALS AND METHODS: Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture...
June 20, 2017: Journal of Ethnopharmacology
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