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immune signature

Christelle Langevin, Jean-Pierre Levraud, Pierre Boudinot
Tripartite motif (TRIM) family or RBCC proteins comprises characteristic zinc-binding domains (a RING (R), a B-box type 1 (B1) and a B-box type 2 (B2)) and coiled-coil (CC) domain followed by a C-terminus variable domain. There are about 80 different TRIM proteins in human, but more than 200 in zebrafish with several large gene expansions (ftr >70 genes; btr >30 genes; trim35 > 30 genes). Repertoires of trim genes in fish are variable across fishes, but they have been remarkably diversified independently in a number of species...
December 11, 2018: Fish & Shellfish Immunology
Ying Li, Kai Yang, Ke Li, He Liu, Siqi Zhao, Mingli Jiao, Xinru Fu
Bladder urothelial carcinoma (BLCA) is a common malignancy with high heterogeneity. A reasonable molecular subtyping can facilitate biological study and personalized therapy of BLCA. In this study, unsupervised consensus clustering was used to acquire the molecular subtypes of BLCA based on messenger RNA (mRNA) and microRNA (miRNA) data. Gene signature markers and canonical signaling pathways were compared between different subtypes. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for the functional annotation of overexpressed genes in different subtypes for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways...
December 12, 2018: Journal of Cellular Biochemistry
Joanna Walkowska, Thomas Kallemose, Göran Jönsson, Mats Jönsson, Ove Andersen, Mads Hald Andersen, Inge Marie Svane, Anne Langkilde, Mef Nilbert, Christina Therkildsen
Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors...
2019: Oncoimmunology
Frederick S Varn, Yue Wang, Chao Cheng
Immune checkpoint inhibitors have shown great potential in treating solid tumors, inducing durable remission and prolonged survival time in responders. Despite their promise, a large fraction of patients remains unresponsive to these treatments highlighting the need for biomarkers that can predict patient sensitivity. Pre-treatment gene expression profiles for patients receiving immune checkpoint inhibitors have recently become available, establishing a new medium by which to discover biomarkers that predict therapy response...
2019: Oncoimmunology
Marion Dajon, Kristina Iribarren, Florent Petitprez, Solenne Marmier, Audrey Lupo, Mélanie Gillard, Hanane Ouakrim, Navas Victor, Di Bartolo Vincenzo, Pierre Emmanuel Joubert, Oliver Kepp, Guido Kroemer, Marco Alifano, Diane Damotte, Isabelle Cremer
In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis...
2019: Oncoimmunology
Katsunobu Hagihara, Stephen Chan, Li Zhang, David Y Oh, Xiao X Wei, Jeffry Simko, Lawrence Fong
Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry...
2019: Oncoimmunology
Magdalena Niedzielska, Elisabeth Israelsson, Bastian Angermann, Benjamin S Sidders, Maryam Clausen, Matthew Catley, Rajneesh Malhotra, Céline Dumont
As we learn more about how immune responses occur in situ , it is becoming clear that each organ/tissue is characterized with its own anatomy and microenvironment which may affect and even determine the outcome of the immune responses. With emerging data from animal studies showing that regulatory T cells infiltrating non-lymphoid tissues exhibit unique phenotypes and transcriptional signatures and display functions beyond their well-established suppressive roles, there is an urgent need to explore the function of tissue Treg cells in humans...
November 16, 2018: Oncotarget
Pramod Darvin, Salman M Toor, Varun Sasidharan Nair, Eyad Elkord
Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment...
December 13, 2018: Experimental & Molecular Medicine
Xinyu Zhang, Ying Hu, Bradley E Aouizerat, Gang Peng, Vincent C Marconi, Michael J Corley, Todd Hulgan, Kendall J Bryant, Hongyu Zhao, John H Krystal, Amy C Justice, Ke Xu
BACKGROUND: The effects of tobacco smoking on epigenome-wide methylation signatures in white blood cells (WBCs) collected from persons living with HIV may have important implications for their immune-related outcomes, including frailty and mortality. The application of a machine learning approach to the analysis of CpG methylation in the epigenome enables the selection of phenotypically relevant features from high-dimensional data. Using this approach, we now report that a set of smoking-associated DNA-methylated CpGs predicts HIV prognosis and mortality in an HIV-positive veteran population...
December 13, 2018: Clinical Epigenetics
Ah Ra Jung, Young-Gyu Eun, Young Chan Lee, Joo Kyung Noh, Kee Hwan Kwon
Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases...
December 12, 2018: International Journal of Molecular Sciences
Chantal Guindi, Alexandre Cloutier, Simon Gaudreau, Echarki Zerif, Patrick P McDonald, Olga Tatsiy, Claude Asselin, Gilles Dupuis, Denis Gris, And Abdelaziz Amrani
Dendritic cells (DCs) play a major role in innate and adaptive immunity and self-immune tolerance. Immunogenic versus tolerogenic DC functions are dictated by their levels of costimulatory molecules and their cytokine expression profile. The transcription factor C/EBPβ regulates the expression of several inflammatory genes in many cell types including macrophages. However, little is known regarding the role of C/EBPβ in tolerogenic versus immunogenic DCs functions. We have previously reported that bone marrow-derived DCs generated with GM-CSF (GM/DCs) acquire the signature of semi-mature tolerogenic IL-10-producing DCs as opposed to immunogenic DCs generated with GM-CSF and IL-4 (IL-4/DCs)...
December 7, 2018: Cells
Paymann Harirchian, Jerry Lee, Stephanie Hilz, Andrew J Sedgewick, Bethany E Perez White, Michael J Kesling, Thaddeus Mully, Justin Golovato, Matthew Gray, Theodora M Mauro, Elizabeth Purdom, Esther A Kim, Hani Sbitany, Tina Bhutani, Charles J Vaske, Stephen C Benz, Raymond J Cho, Jeffrey B Cheng
Genetic variation in the NFκB inhibitors, ABIN1 and A20, increase risk for psoriasis. While critical for hematopoietic immune cell function, these genes are believed to additionally inhibit psoriasis by dampening inflammatory signaling in keratinocytes. We dissected ABIN1 and A20's regulatory role in human keratinocyte inflammation using an RNA-seq based comparative genomic approach. Here we show subsets of the IL-17 and TNFα signaling pathways are robustly restricted by A20 overexpression. In contrast, ABIN1 overexpression inhibits these genes more modestly for IL-17, and weakly for TNFα...
December 10, 2018: Journal of Investigative Dermatology
Alexander Strachan, Zoe Harrington, Clare McIlwaine, Matthew Jerreat, Louise A Belfield, Aniko Kilar, Simon K Jackson, Andrew Foey, Svetislav Zaric
OBJECTIVES: Regulation of lipopolysaccharide (LPS) chemical composition, particularly its lipid A domain, is an important, naturally occurring mechanism that drives bacteria-host immune system interactions into either a symbiotic or pathogenic relationship. Members of the subgingival oral microbiota can critically modulate host immuno-inflammatory responses by synthesizing different LPS isoforms. The objectives of this study were to analyze subgingival lipid A profiles and endotoxin activities in periodontal health and disease and to evaluate the use of the recombinant factor C assay as a new, lipid A-based biosensor for personalized, point-of-care periodontal therapy...
December 12, 2018: Clinical Oral Investigations
Bin Wu, Kaixuan Wang, Janguo Fei, Yi Bao, Xiaoguang Wang, Zhengwei Song, Fei Chen, Jun Gao, Zhengxiang Zhong
A growing body of evidence confirms that long non‑coding RNAs (lncRNAs) have an important role in biological processes by regulating gene expression at multiple levels. Dysregulated lncRNAs may be potential prognostic biomarkers or targets for the development of cancer treatments. However, the prognostic role of an lncRNA signature in pancreatic cancer has not been investigated. Pancreatic cancer lncRNA expression profiles from The Cancer Genome Atlas (TCGA) were analyzed in the current study. The prognostic value of differentially expressed lncRNAs (DElncRNAs) was evaluated via the Kaplan‑Meier method...
October 3, 2018: Oncology Reports
Yael Haberman, Melanie Schirmer, Phillip J Dexheimer, Rebekah Karns, Tzipi Braun, Mi-Ok Kim, Thomas D Walters, Robert N Baldassano, Joshua D Noe, Joel Rosh, James Markowitz, Wallace V Crandall, David R Mack, Anne M Griffiths, Melvin B Heyman, Susan S Baker, Richard Kellermayer, Dedrick Moulton, Ashish S Patel, Ajay S Gulati, Steven J Steiner, Neal LeLeiko, Anthony Otley, Maria Oliva-Hemker, David Ziring, Barbara S Kirschner, David J Keljo, Stephen L Guthery, Stanley A Cohen, Scott Snapper, Jonathan Evans, Marla Dubinsky, Bruce Aronow, Jeffrey S Hyams, Subra Kugathasan, Curtis Huttenhower, Ramnik J Xavier, Lee A Denson
Age-of-diagnosis associated variation in disease location and antimicrobial sero-reactivity has suggested fundamental differences in pediatric Crohn Disease (CD) pathogenesis. This variation may be related to pubertal peak incidence of ileal involvement and Peyer's patches maturation, represented by IFNγ-expressing Th1 cells. However, direct mucosal evidence is lacking. We characterize the global pattern of ileal gene expression and microbial communities in 525 treatment-naive pediatric CD patients and controls (Ctl), stratifying samples by their age-of-diagnosis...
December 12, 2018: Mucosal Immunology
Yitian Xu, Lu Huang, Jonathan L Kirschman, Daryll A Vanover, Pooja M Tiwari, Philip J Santangelo, Xiling Shen, David G Russell
Therapeutic strategies based on in vitro-transcribed mRNA (IVT) are attractive because they avoid the permanent signature of genomic integration that is associated with DNA-based therapy and result in the transient production of proteins of interest. To date, IVT has mainly been used in vaccination protocols to generate immune responses to foreign Ags. In this "proof-of-principle" study, we explore a strategy of combinatorial IVT to recruit and reprogram immune effector cells to acquire divergent biological functions in mice in vivo...
December 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Norikatsu Miyoshi, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
The classical cancer therapies, including chemotherapy and radiation therapy, can initially show good results and tumor shrinkage; however, for most cancer patients disease recurrence is a common event. This tumor regrowth following therapy is now thought to depend on a small population of cancer stem cells (CSCs), which, similar to other stem cells, have the capacity for self-renewal and multipotent differentiation. Cancer stem cells have been identified based on cell surface protein expression in many tumor types, and for all diseases studied, this specific cell population is required for serial transplantation in animal models...
December 12, 2018: Japanese Journal of Clinical Oncology
Ulrike Strittmatter-Keller, Caroline Walter, Celine Rauld, Nicole Egli, Camille Regairaz, Sabine Rabe, Gerhard Zenke, José Carballido, Tamás Schweighoffer
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact...
2018: PloS One
Hiroshi Nishi, Tanya N Mayadas
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease characterized by IgG-autoantibodies to nuclear antigens that can deposit in the kidney and trigger lupus nephritis. Neutrophils accumulate in the kidneys of patients with proliferative LUPUS NEPHRITIS and neutrophil products and a subset of granulocytes, called low-density granulocytes (LDG) may contribute to lupus nephritis pathogenesis. Here, we will discuss recent studies implicating neutrophils in the pathogenesis of human SLE nephritis and then examine studies that provide mechanistic insights into how these cells are recruited to the glomerulus following immune complex deposition and how their products may promote lupus nephritis...
December 11, 2018: Current Opinion in Rheumatology
Hara Levy, Shuang Jia, Amy Pan, Xi Zhang, Mary L Kaldunski, Melodee L Nugent, Melissa Reske, Rachel A Feliciano, Diana Quintero, Michael M Renda, Katherine J Woods, Kathy Murkowski, Keven Johnson, James Verbsky, Trivikram Dasu, Justin Eze Ideozu, Susanna McColley, Michael W Quasney, Mary K Dahmer, Ellis D Avner, Philip M Farrell, Carolyn L Cannon, Howard Jacob, Pippa M Simpson, Martin J Hessner
Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and development of inflammation and progression of lung disease are not fully understood, limiting our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status using plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients (n=103) and unrelated, healthy controls (n=31)...
December 12, 2018: Physiological Genomics
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