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cellular immune

Ulrich Jarry, Noémie Joalland, Cynthia Chauvin, Béatrice Clemenceau, Claire Pecqueur, Emmanuel Scotet
Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain cancer in adults, is generally associated with a poor prognosis, and scarce efficient therapies have been proposed over the last decade. Among the promising candidates for designing novel therapeutic strategies, cellular immunotherapies have been targeted to eliminate highly invasive and chemo-radioresistant tumor cells, likely involved in a rapid and fatal relapse of this cancer. Thus, administration(s) of allogeneic GBM-reactive immune cell effectors, such as human Vϒ9Vδ2 T lymphocytes, in the vicinity of the tumor would represents a unique opportunity to deliver efficient and highly concentrated therapeutic agents directly into the site of brain malignancies...
September 1, 2018: Journal of Visualized Experiments: JoVE
Ian Restall, Danielle Anne Bozek, Charles Chesnelong, Samuel Weiss, H Artee Luchman
Glioblastoma (GBM) is an aggressive brain tumor that is poorly controlled with the currently available treatment options. Key features of GBMs include rapid proliferation and pervasive invasion into the normal brain. Recurrence is thought to result from the presence of radio- and chemo-resistant brain tumor stem cells (BTSCs) that invade away from the initial cancerous mass and, thus, evade surgical resection. Hence, therapies that target BTSCs and their invasive abilities may improve the otherwise poor prognosis of this disease...
August 29, 2018: Journal of Visualized Experiments: JoVE
Miwa Hayashi, Kengo Kuroda, Kohei Ihara, Takahiro Iwaya, Emiko Isogai
Antimicrobial peptides (AMPs) are multifunctional factors with an important role in the innate immune system. Our previous studies revealed that the human cathelicidin LL‑37 and its analog, FF/CAP18, limit the proliferation of colon cancer cell lines. In the present study, the exosomes released by HCT116 cells treated with FF/CAP18 were analyzed. After the treatment, exosomes were isolated from the culture supernatant by ultrafiltration and using the miRCURY™ Exosome Isolation Kit. Membrane vesicles 40‑100‑nm expressing CD63 and CD81 were identified before and after FF/CAP18 treatment...
September 13, 2018: International Journal of Molecular Medicine
Jiao Dai, Liying Lai, Huanyu Tang, Weixue Wang, Shuoyue Wang, Chengping Lu, Huochun Yao, Hongjie Fan, Zongfu Wu
Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5'-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5'-nucleotidase not only enables producing 2'-deoxyadenosine from 2'-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2'-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses...
September 16, 2018: Virulence
Yi Yang, Di Sun, Ji Zhou, Chensheng Tan, Hong Zhang, ZhengRong Chen, ChuangLi Hao, Jinping Zhang
Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T cell function. In mice, MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have shown that injection of a lethal or sublethal dose of LPS into mice could result in the expansion of MDSCs in the bone marrow(BM), spleen and blood. Until now, the molecular mechanisms responsible for this expansion are poorly studied; specifically, the roles of the individual microRNAs (miRNAs) which may be involved remain largely unknown...
September 17, 2018: Immunology and Cell Biology
Henry Hirschberg, Kristian Berg, Qian Peng
Photodynamic therapy of tumors requires the topical, systemic or oral administration of a photosensitizing compound, illumination of the tumor area by light of a specific wavelength and the presence of oxygen. Light activation of the photosensitizer transfers energy to molecular oxygen creating singlet oxygen, a highly reactive and toxic species that rapidly reacts with cellular components causing oxidative damage, ultimately leading to cell death. Tumor destruction caused by photodynamic therapy is not only a result of direct tumor cell toxicity via the generation of reactive oxygen species but there is also an immunological and vascular component involved...
2018: Neuroimmunology and Neuroinflammation
Laura E Johnson, Dirk Brockstedt, Meredith Leong, Peter Lauer, Erin Theisen, John-Demian Sauer, Douglas G McNeel
Background . Sipuleucel T, an autologous cell-based vaccine targeting prostatic acid phosphatase (PAP), has demonstrated efficacy for the treatment of advanced prostate cancer. DNA vaccines encoding PAP and live attenuated Listeria vaccines have entered clinical trials for patients with prostate cancer, and have advantages in terms of eliciting predominantly Th1-biased immunity. In this study, we investigated whether the immunogenicity and anti-tumor efficacy of a DNA and Listeria vaccine, each encoding PAP, could be enhanced by using them in a heterologous prime/boost approach...
2018: Oncoimmunology
Peng Zhu, Carl Atkinson, Suraj Dixit, Qi Cheng, Danh Tran, Kunal Patel, Yu-Lin Jiang, Scott Esckilsen, Kayla Miller, Grace Bazzle, Patterson Allen, Alfred Moore, Ann-Marie Broome, Satish N Nadig
Hypothermic preservation is the standard of care for storing organs prior to transplantation. Endothelial and epithelial injury associated with hypothermic storage causes downstream graft injury and, as such, the choice of an ideal donor organ preservation solution remains controversial. Cold storage solutions, by design, minimize cellular necrosis and optimize cellular osmotic potential, but do little to assuage immunological cell activation or immune cell priming post transplantation. Thus, here we explore the efficacy of our previously described novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care University of Wisconsin preservation solution as a means to alter the immunological microenvironment post transplantation using in vivo models of tracheal and aortic allograft transplantation...
July 23, 2018: RSC Advances
Lorenzo Galluzzi, Stefani Spranger, Elaine Fuchs, Alejandro López-Soto
Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy...
September 13, 2018: Trends in Cell Biology
Kjeld C Engvild
Almost all solid tumors consist of aneuploid cells with highly abnormal chromosome numbers. Such cancer cells could very well originate from chromosome missegregation which is a disturbingly common phenomenon, happening in 0.01 to 4 percent of cell divisions. Missegregated cells are aneuploid, typically lacking a chromosome or having one in surplus. Missegregated cells have mutation in the gene dose of the perhaps a thousand genes on a chromosome in one step. After missegregation cell division cannot be done right, as at least one daughter cell has a faulty chromosome number...
November 2018: Medical Hypotheses
Jennifer Kurz, Robert Brunkhorst, Christian Foerch, Leonard Blum, Marina Henke, Laureen Gabriel, Thomas Ulshöfer, Nerea Ferreirós, Michael J Parnham, Gerd Geisslinger, Susanne Schiffmann
Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion of CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. In the present study, we investigated the importance of Cers and their synthesizing/metabolizing enzymes in MS...
September 14, 2018: Clinical Science (1979-)
Kai Luo, Jun Di, Panpan Han, Shuhuan Zhang, Lihai Xia, Guangming Tian, Wenbing Zhang, Dan Dun, Qiaoqing Xu, Qiwei Wei
Dabry's sturgeon (Acipenser dabryanus), as a living fossil, is considered a critically endangered aquatic animal in China. To date, the immune system of this species remains largely unknown, with limited available sequence information. In addition, increasing incidence of bacterial pathogenic diseases has been reported. Hence, the present study aimed to characterize comprehensively transcriptome profile of the head kidney from Dabry's sturgeon infected with Aeromonas hydrophila using Illumina platform. Over 42 million high-quality reads were obtained and de novo assembled into a final set of 195240 unique transcript fragments (unigenes), with an average length of 564 bp...
September 13, 2018: Fish & Shellfish Immunology
Rebecca K Carrell, Rebecca A Stanton, Stephen P Ethier, Amanda C LaRue, Adam C Soloff
Cellular immunity established via immunotherapy holds the potential to eliminate solid tumors. Yet, cancer vaccines have failed to induce tumor-reactive T cells of sufficient quality to control disease. The inducible T cell costimulator (ICOS) pathway has been implicated in both the selective induction of immunity over tolerance as well as licensing of IL-17-polarized cellular immunity. Herein, we evaluated the ability of ICOS ligand (ICOSL) to augment the immunogenicity of adenoviral-based vaccination targeting the unglycosylated MUC1 peptide antigen...
September 12, 2018: Vaccine
Dhadhang Wahyu Kurniawan, Arun Kumar Jajoriya, Garima Dhawan, Divya Mishra, Josepmaria Argemi, Ramon Bataller, Gert Storm, Durga Prasad Mishra, Jai Prakash, Ruchi Bansal
Non-alcoholic steatohepatitis (NASH) is the leading cause of cirrhosis worldwide and the most rapidly growing indication for liver transplantation. Macrophages are the important cellular component in the inflammatory milieu in NASH. Inflammatory and pro-fibrotic mediators produced by macrophages causes significant tissue injury in many inflammatory diseases. Therefore, inhibition of the inflammatory macrophages would be a promising approach to attenuate NASH. In this study, we studied the implication of SYK pathway in NASH, and investigated PLGA nanoparticles-based delivery of SYK pathway inhibitor as an effective and promising therapeutic approach for the treatment of NASH...
September 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Anne Grünewald, Kishore R Kumar, Carolyn M Sue
New discoveries providing insights into mitochondrial bioenergetics, their dynamic interactions as well as their role in cellular homeostasis have dramatically advanced our understanding of the neurodegenerative process of Parkinson's disease (PD). Respiratory chain impairment is a key feature in sporadic PD patients and there is growing evidence that links proteins encoded by PD-associated genes to disturbances in mitochondrial function. Against the backdrop of latest advances in the development of PD treatments that target mitochondria, we aim to give an overview of the literature published in the last three decades on the significance of mitochondria in the pathogenesis of PD...
September 13, 2018: Progress in Neurobiology
Guizhong Zhang, Xin Li, Lvyan Liu, Junxin Li, Qian Chen, Shiran Huang, Yutao Li, Xiaochun Wan
BACKGROUND: Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccines. Therefore, safe and effective HBV vaccines are still clinically needed. METHODS: In this study, we developed a plasmid DNA vaccine encoding CD317 single-chain fragment variable (α317scFv) linked with the hepatitis B surface antigen (HBsAg) and detected the humoral and cellular immune responses elicited by this vaccine in BALB/c mice...
September 13, 2018: Biochemical and Biophysical Research Communications
Debora Scaldaferri, Annalisa Bosi, Marco Fabbri, Edoardo Pedrini, Antonio Inforzato, Roberto Valli, Annalisa Frattini, Annarosaria De Vito, Douglas M Noonan, Roberto Taramelli, Lorenzo Mortara, Francesco Acquati
Macrophages represent key inflammatory cellular effectors of the innate immune response. Despite being widely acknowledged as professional phagocytes, the functional roles played by these cells have been progressively widened over the years to encompass regulation of the adaptive immune system, stimulation or suppression of cancer cell growth and tissue remodeling. These diverse functional features have led to the concept of "macrophage plasticity", i.e. the ability of these cells to express a wide range of phenotypes endowed with different functional roles...
September 12, 2018: Immunology Letters
Jasmine Tomar, Harshad P Patil, Gustavo Bracho, Wouter F Tonnis, Henderik W Frijlink, Nikolai Petrovsky, Rita Vanbever, Anke Huckriede, Wouter L J Hinrichs
Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5 μm) suitable for inhalation...
September 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Cancan Lyu, So Jin Bing, Wambui S Wandu, Biying Xu, Guangpu Shi, Samuel J Hinshaw, Mercedes Lobera, Rachel R Caspi, Lin Lu, Jianfei Yang, Igal Gery
EAU, an animal model for severe intraocular inflammatory eye diseases, is mediated by both Th1 and Th17 cells. Here, we examined the capacity of TMP778, a selective inhibitor of RORγt, to inhibit the development of EAU, as well as the related immune responses. EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Treatment with TMP778 significantly inhibited the development of EAU, determined by histological examination. In addition, the treatment suppressed the cellular immune response to IRBP, determined by reduced production of IL-17 and IFN-γ, as well as lower percentages of lymphocytes expressing these cytokines, as compared to vehicle-treated controls...
September 15, 2018: European Journal of Immunology
Valentina Damato, Bettina Balint, Anne-Kathrin Kienzler, Sarosh R Irani
An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody-mediated movement disorders, and outline increasingly well-established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation...
September 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
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