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https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#1
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#2
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-nk-cell-anti-leukemia-and-fc%C3%AE-riiia-triggered-responses
#3
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate following short-term pre-activation with interleukin (IL)-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks following the initial pre-activation. Conventional NK cell function is dependent upon a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27893813/azidothymidine-sensitizes-primary-effusion-lymphoma-cells-to-kaposi-sarcoma-associated-herpesvirus-specific-cd4-t-cell-control-and-inhibits-virf3-function
#4
Samantha J Williamson, Samantha M Nicol, Michael Stürzl, Shereen Sabbah, Andrew D Hislop
Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#5
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#6
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27880900/tailored-tumor-immunogenicity-reveals-regulation-of-cd4-and-cd8%C3%A2-t-cell-responses-against-cancer
#7
Sarah Knocke, Bettina Fleischmann-Mundt, Michael Saborowski, Michael P Manns, Florian Kühnel, Thomas C Wirth, Norman Woller
CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the interplay of both cell types and their role in tumor suppression still remain elusive. In this study, we investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse models. Tumors were induced in p19Arf-deficient mice by hydrodynamic injection of transposon plasmids encoding NrasG12V and pre-defined tumor antigens. This allowed for assessing the regulation of tumor-specific CD4 and CD8 T cell responses...
November 22, 2016: Cell Reports
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
#8
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/27872213/autocrine-type-i-ifn-signaling-in-dendritic-cells-stimulated-with-fungal-%C3%AE-glucans-or-lipopolysaccharide-promotes-cd8-t-cell-activation
#9
Nargess Hassanzadeh-Kiabi, Alberto Yáñez, Ivy Dang, Gislâine A Martins, David M Underhill, Helen S Goodridge
Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal β-glucans stimulate IFN-β production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of β-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal β-glucan particle-stimulated DCs...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27862100/role-of-epigenetic-modification-and-immunomodulation-in-a-murine-prostate-cancer-model
#10
Jay E Sulek, Samuel P Robinson, Albert A Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H Manjili, Amir Toor, Georgi Guruli
INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC)...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27861124/rab22a-controls-mhc-i-intracellular-trafficking-and-antigen-cross-presentation-by-dendritic-cells
#11
Ignacio Cebrian, Cristina Croce, Néstor A Guerrero, Nicolas Blanchard, Luis S Mayorga
Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8(+) T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e., Toxoplasma gondii) and tumors. To achieve efficient cross-presentation, dendritic cells (DCs) have specialized endocytic pathways; however, the molecular effectors involved are poorly understood. In this work, we identify the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27855702/tumor-immune-microenvironment-characterization-in-clear-cell-renal-cell-carcinoma-identifies-prognostic-and-immunotherapeutically-relevant-messenger-rna-signatures
#12
Yasin Şenbabaoğlu, Ron S Gejman, Andrew G Winer, Ming Liu, Eliezer M Van Allen, Guillermo de Velasco, Diana Miao, Irina Ostrovnaya, Esther Drill, Augustin Luna, Nils Weinhold, William Lee, Brandon J Manley, Danny N Khalil, Samuel D Kaffenberger, Yingbei Chen, Ludmila Danilova, Martin H Voss, Jonathan A Coleman, Paul Russo, Victor E Reuter, Timothy A Chan, Emily H Cheng, David A Scheinberg, Ming O Li, Toni K Choueiri, James J Hsieh, Chris Sander, A Ari Hakimi
BACKGROUND: Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. RESULTS: We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores...
November 17, 2016: Genome Biology
https://www.readbyqxmd.com/read/27853651/gucy2c-directed-car-t-cells-oppose-colorectal-cancer-metastases-without-autoimmunity
#13
Michael S Magee, Crystal L Kraft, Tara S Abraham, Trevor R Baybutt, Glen P Marszalowicz, Peng Li, Scott A Waldman, Adam E Snook
Adoptive T-cell therapy (ACT) is an emerging paradigm in which T cells are genetically modified to target cancer-associated antigens and eradicate tumors. However, challenges treating epithelial cancers with ACT reflect antigen targets that are not tumor-specific, permitting immune damage to normal tissues, and preclinical testing in artificial xenogeneic models, preventing prediction of toxicities in patients. In that context, mucosa-restricted antigens expressed by cancers exploit anatomical compartmentalization which shields mucosae from systemic antitumor immunity...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27835636/in-vitro-evaluation-of-the-biological-responses-of-canine-macrophages-challenged-with-plga-nanoparticles-containing-monophosphoryl-lipid-a
#14
Delphine Guldner, Julianne K Hwang, Maria Clara D Cardieri, Meaghan Eren, Parissa Ziaei, M Grant Norton, Cleverson D Souza
Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been considerably studied as a promising biodegradable delivery system to induce effective immune responses and to improve stability, safety, and cost effectiveness of vaccines. The study aimed at evaluating early inflammatory effects and cellular safety of PLGA NPs, co-encapsulating ovalbumin (PLGA/OVA NPs), as a model antigen and the adjuvant monophosphoryl lipid A (PLGA/MPLA NPs) as an adjuvant, on primary canine macrophages. The PLGA NPs constructs were prepared following the emulsion-solvent evaporation technique and further physic-chemically characterized...
2016: PloS One
https://www.readbyqxmd.com/read/27835581/regulatory-landscape-and-clinical-implication-of-mbd3-in-human-malignant-glioma
#15
Yi Cui, Jian Li, Ling Weng, Sara E Wirbisky, Jennifer L Freeman, Jingping Liu, Qing Liu, Xianrui Yuan, Joseph Irudayaraj
In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826664/anti-her2-cd4-t-helper-type-1-immune-response-is-superior-to-breast-mri-for-assessing-response-to-neoadjuvant-therapy-in-patients-with-her2-positive-breast-cancer
#16
Lucy M De La Cruz, Elizabeth S McDonald, R Mick, Jashodeep Datta, Nadia F Nocera, Shuwen Xu, Carla S Fisher, Brian J Czerniecki
BACKGROUND: In human epidermal growth factor 2-positive breast cancer (HER2(+)BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2(+)BC patients...
November 8, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27821490/suppression-of-type-i-ifn-signaling-in-tumors-mediates-resistance-to-anti-pd-1-treatment-that-can-be-overcome-by-radiotherapy
#17
Xiaohong Wang, Jonathan E Schoenhals, Ailin Li, David R Valdecanas, Huiping Ye, Fenglin Zhang, Chad Tang, Ming Tang, Chang-Gong Liu, Xiuping Liu, Sunil Krishnan, James P Allison, Padmanee Sharma, Patrick Hwu, Ritsuko Komaki, Willem W Overwijk, Daniel R Gomez, Joe Y Chang, Stephen M Hahn, Maria Angelica Cortez, James W Welsh
Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PDL1 (CD274) expression did not differ between the resistant and parental tumor cells...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27816827/in-silico-designing-breast-cancer-peptide-vaccine-for-binding-to-mhc-class-i-and-ii-a-molecular-docking-study
#18
Manijeh Mahdavi, Violaine Moreau
Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III...
October 19, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27815442/vegf-requires-the-receptor-nrp-1-to-inhibit-lipopolysaccharide-dependent-dendritic-cell-maturation
#19
Nougboli A E Oussa, Amina Dahmani, Marie Gomis, Manon Richaud, Emil Andreev, Ali-Reza Navab-Daneshmand, Julie Taillefer, Cédric Carli, Salix Boulet, Laurent Sabbagh, Nathalie Labrecque, Przemyslaw Sapieha, Jean-Sébastien Delisle
To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the integration of several cellular stimulatory or inhibitory signals. The soluble factors and their receptors controlling this central aspect of DC biology are incompletely characterized...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27815354/cytokine-induced-killer-cells-kill-chemo-surviving-melanoma-cancer-stem-cells
#20
Dario Sangiolo, Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Giulia Mesiano, Ramona Rotolo, Francesco Sassi, Martina Sanlorenzo, Alessandro Zaccagna, Alberto Pisacane, Rebecca Senetta, Michela Cangemi, Giulia Cattaneo, Valentina Martin, Valentina Coha, Susanna Gallo, Ymera Pignochino, Anna Sapino, Giovanni Grignani, Fabrizio Carnevale-Schianca, Massimo Aglietta
PURPOSE: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSCs) was explored, as CSCs are considered responsible for chemo-resistance and relapses. EXPERIMENTAL DESIGN: Putative mCSCs were visualized by engineering patient-derived melanoma cells (MCs) with a lentiviral-vector encoding eGFP under expression control by stemness gene promoter oct4. Their stemness potential was confirmed in vivo by limiting dilution assays...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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