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Immunogenomics

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https://www.readbyqxmd.com/read/28322934/comparative-immunogenomics-of-molluscs
#1
Jonathan H Schultz, Coen M Adema
Comparative immunology, studying both vertebrates and invertebrates, provided the earliest descriptions of phagocytosis as a general immune mechanism. However, the large scale of animal diversity challenges all-inclusive investigations and the field of immunology has developed by mostly emphasizing study of a few vertebrate species. In addressing the lack of comprehensive understanding of animal immunity, especially that of invertebrates, comparative immunology helps toward management of invertebrates that are food sources, agricultural pests, pathogens, or transmit diseases, and helps interpret the evolution of animal immunity...
March 18, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28278192/pbmc-transcriptome-profiles-identifies-potential-candidate-genes-and-functional-networks-controlling-the-innate-and-the-adaptive-immune-response-to-prrsv-vaccine-in-pietrain-pig
#2
Md Aminul Islam, Christine Große-Brinkhaus, Maren Julia Pröll, Muhammad Jasim Uddin, Sharmin Aqter Rony, Dawit Tesfaye, Ernst Tholen, Michael Hoelker, Karl Schellander, Christiane Neuhoff
The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination. Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#3
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28187283/applications-of-immunogenomics-to-cancer
#4
REVIEW
X Shirley Liu, Elaine R Mardis
Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28175395/143%C3%A2-identification-of-neoantigen-specific-cd8-t-cells-in-two-murine-orthotopic-glioblastoma-models-using-cancer-immunogenomics
#5
Tanner M Johanns, Jeffrey Ward, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Maxim N Artyomov, Chris A Miller, Elaine R Mardis, Gavin P Dunn
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#6
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28048236/su-f-r-01-preclinical-radioimmunogenomics-study-to-design-personalized-radiotherapy
#7
H Abdollahi
PURPOSE: Radiogenomics is an active area of research to find clinical correlation between genomics and radiotherapy outcomes. In this era, many different biological issues should be taken into account. In this study we aimed to introduce "Radioimmunogenomics" as a new approach to study immunogetics issue regard to radiotherapy induced clinical manifestations. METHODS: We studied different immunological pathways and signaling molecules which underling radiation response of normal and malignant tissues...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27828772/toward-a-reference-gene-catalog-of-human-primary-monocytes
#8
Hoda Mirsafian, Adiratna Mat Ripen, Thamilvaani Manaharan, Saharuddin Bin Mohamad, Amir Feisal Merican
Transcriptome analyses based on high-throughput RNA sequencing (RNA-Seq) provide powerful and quantitative characterization of cell types and in-depth understanding of biological systems in health and disease. In this study, we present a comprehensive transcriptome profile of human primary monocytes, a crucial component of the innate immune system. We performed deep RNA-Seq of monocytes from six healthy subjects and integrated our data with 10 other publicly available RNA-Seq datasets of human monocytes. A total of 1...
November 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27799140/endogenous-neoantigen-specific-cd8-t-cells-identified-in-two-glioblastoma-models-using-a-cancer-immunogenomics-approach
#9
Tanner M Johanns, Jeffrey P Ward, Christopher A Miller, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Elaine R Mardis, Maxim N Artyomov, Robert D Schreiber, Gavin P Dunn
The "cancer immunogenomics" paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole-exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. GL261 and SMA-560 harbored 4,932 and 2,171 nonsynonymous exome mutations, respectively, of which less than half were expressed...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27683556/immunogenomics-of-hypermutated-glioblastoma-a-patient-with-germline-pole-deficiency-treated-with-checkpoint-blockade-immunotherapy
#10
Tanner M Johanns, Christopher A Miller, Ian G Dorward, Christina Tsien, Edward Chang, Arie Perry, Ravindra Uppaluri, Cole Ferguson, Robert E Schmidt, Sonika Dahiya, George Ansstas, Elaine R Mardis, Gavin P Dunn
We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment...
November 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27531490/immunogenomic-engineering-of-a-plug-and-dis-play-hybridoma-platform
#11
Mark Pogson, Cristina Parola, William J Kelton, Paul Heuberger, Sai T Reddy
Hybridomas, fusions of primary mouse B cells and myelomas, are stable, rapidly-proliferating cell lines widely utilized for antibody screening and production. Antibody specificity of a hybridoma clone is determined by the immunoglobulin sequence of the primary B cell. Here we report a platform for rapid reprogramming of hybridoma antibody specificity by immunogenomic engineering. Here we use CRISPR-Cas9 to generate double-stranded breaks in immunoglobulin loci, enabling deletion of the native variable light chain and replacement of the endogenous variable heavy chain with a fluorescent reporter protein (mRuby)...
2016: Nature Communications
https://www.readbyqxmd.com/read/27516546/network-pharmacology-of-jak-inhibitors
#12
Devapregasan Moodley, Hideyuki Yoshida, Sara Mostafavi, Natasha Asinovski, Adriana Ortiz-Lopez, Peter Symanowicz, Jean-Baptiste Telliez, Martin Hegen, James D Clark, Diane Mathis, Christophe Benoist
Small-molecule inhibitors of the Janus kinase family (JAKis) are clinically efficacious in multiple autoimmune diseases, albeit with increased risk of certain infections. Their precise mechanism of action is unclear, with JAKs being signaling hubs for several cytokines. We assessed the in vivo impact of pan- and isoform-specific JAKi in mice by immunologic and genomic profiling. Effects were broad across the immunogenomic network, with overlap between inhibitors. Natural killer (NK) cell and macrophage homeostasis were most immediately perturbed, with network-level analysis revealing a rewiring of coregulated modules of NK cell transcripts...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27399422/143%C3%A2-identification-of-neoantigen-specific-cd8-t-cells-in-two-murine-orthotopic-glioblastoma-models-using-cancer-immunogenomics
#13
Tanner M Johanns, Jeffrey Ward, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Maxim N Artyomov, Chris A Miller, Elaine R Mardis, Gavin P Dunn
INTRODUCTION: Our understanding of how immune-based strategies designed to enhance T-cell activation might effectively control glioblastoma progression has been limited by our ability to identify and monitor tumor-specific T cells. The "cancer immunogenomics" approach has facilitated the search for tumor-specific antigens over the past 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in preclinical brain tumor models susceptible to checkpoint immunotherapy...
August 2016: Neurosurgery
https://www.readbyqxmd.com/read/27387842/immunogenomics-of-gastrointestinal-nematode-infection-in-ruminants-breeding-for-resistance-to-produce-food-sustainably-and-safely
#14
REVIEW
T Sweeney, J P Hanrahan, M T Ryan, B Good
Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment...
September 2016: Parasite Immunology
https://www.readbyqxmd.com/read/27297497/vdjviz-a-versatile-browser-for-immunogenomics-data
#15
Dmitriy V Bagaev, Ivan V Zvyagin, Ekaterina V Putintseva, Mark Izraelson, Olga V Britanova, Dmitriy M Chudakov, Mikhail Shugay
BACKGROUND: The repertoire of T- and B-cell receptor sequences encodes the antigen specificity of adaptive immunity system, determines its present state and guides its ability to mount effective response against encountered antigens in future. High throughput sequencing of immune repertoires (Rep-Seq) is a promising technique that allows to profile millions of antigen receptors of an individual in a single experiment. While a substantial number of tools for mapping and assembling Rep-Seq data were published recently, the field still lacks an intuitive and flexible tool that can be used by researchers with little or no computational background for in-depth analysis of immune repertoire profiles...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27153063/a-brief-review-of-computer-assisted-approaches-to-rational-design-of-peptide-vaccines
#16
REVIEW
Ashesh Nandy, Subhash C Basak
The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages...
May 4, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27084102/cytokine-like-1-chemoattracts-monocytes-macrophages-via-ccr2
#17
Xiaolin Wang, Ting Li, Wenyan Wang, Wanqiong Yuan, Huihui Liu, Yingying Cheng, Pingzhang Wang, Yu Zhang, Wenling Han
Cytokine-like 1 (CYTL1) is a novel potential cytokine that was first identified in CD34(+) cells derived from bone marrow and cord blood, and it was also found using our immunogenomics strategy. The immunobiological functions of CYTL1 remain largely unknown, and its potential receptor(s) has not been identified. A previous proposed hypothesis suggested that CYTL1 had structural similarities with CCL2 and that CCR2 was a potential receptor of CYTL1. In this study, we verify that CYTL1 possesses chemotactic activity and demonstrate that its functional receptor is CCR2B using a series of experiments performed in HEK293 cells expressing CCR2B or CCR2B-EGFP, including chemotaxis, receptor internalization, and radioactive binding assays...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27070898/harnessing-the-immune-system-for-the-treatment-of-melanoma-current-status-and-future-prospects
#18
Andrea Guennoun, Heba Sidahmed, Cristina Maccalli, Barbara Seliger, Francesco M Marincola, Davide Bedognetti
When malignant melanoma is diagnosed early, surgical resection is the intervention of choice and is often curative, but many patients present with unresectable disease at later stages. Due to its complex etiology paired with well-documented chemoresistance and high metastatic potential, patients with advanced melanoma had a poor prognosis, and the treatment of this disease remained unsatisfactory for many years. Recently, targeted therapy, immune checkpoint inhibition, or combinatory approaches have revolutionized the therapeutic options of melanoma allowing considerable improvement in disease control and survival...
August 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/26934552/immunogenomics-reveal-molecular-circuits-of-diclofenac-induced-liver-injury-in-mice
#19
Eun-Hee Lee, Jung-Hwa Oh, Saravanakumar Selvaraj, Se-Myo Park, Mi-Sun Choi, Reinhard Spanel, Seokjoo Yoon, Jürgen Borlak
Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis...
March 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/26819449/pan-cancer-immunogenomic-perspective-on-the-tumor-microenvironment-based-on-pd-l1-and-cd8-t-cell-infiltration
#20
Chan-Young Ock, Bhumsuk Keam, Sehui Kim, Ju-Seog Lee, Miso Kim, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo
PURPOSE: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors. EXPERIMENTAL DESIGN: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed...
May 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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