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Immunogenomics

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https://www.readbyqxmd.com/read/29762641/functional-genomics-paving-the-way-for-more-successful-cancer-immunotherapy
#1
Reham Ajina, Danielle Zamalin, Louis M Weiner
Immunotherapies have revolutionized cancer treatment. Immunotherapy is effective for the treatment of a wide range of cancer types and can mediate complete and durable tumor regression. Nonetheless, the field still faces many significant challenges, such as the need for personalized therapeutic strategies and better biomarkers, the difficulty of selecting the right combination therapy, and resistance to currently available immunotherapies. Both cancer and host immunity comprise significantly diverse and complex ecosystems, making immunogenomics an ideal field for functional genomics analysis...
May 11, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29736822/immunogenomic-screening-approach-to-identify-new-antigens-for-the-serological-diagnosis-of-chronic-chagas-disease
#2
Rutyanne Maria Tonelli Elisei, Christiane Santos Matos, Ana Maria Ravena Severino Carvalho, Ana Thereza Chaves, Fernanda Alvarenga Cardoso Medeiros, Ronaldo Barbosa, Andreza Pain Marcelino, Kenia Dos Santos Emidio, Eduardo Antonio Ferraz Coelho, Mariana Costa Duarte, Tiago Antônio de Oliveira Mendes, Manoel Otávio da Costa Rocha, Daniel Menezes-Souza
Serological tests are preferentially used for the diagnosis of Chagas' disease (CD) during the chronic phase because of the low parasitemia and high anti-Trypanosoma cruzi antibody titers. However, the current methods showed several disadvantages, as contradictory or inconclusive results, mainly related to the characteristics of the antigens used, in general, crude or whole parasites, but also due to antigen production protocol and the experimental conditions used in serological tests. Thus, better-quality serological assays are urgently needed...
May 7, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29721177/a-pilot-study-of-durvalumab-and-tremelimumab-and-immunogenomic-dynamics-in-metastatic-breast-cancer
#3
Cesar August Santa-Maria, Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Alfred Rademaker, Ami N Shah, Leeaht Gross, Luis Z Blanco, Sarika Jain, Lisa Flaum, Claudia Tellez, Regina Stein, Regina Uthe, William J Gradishar, Massimo Cristofanilli, Yusuke Nakamura, Francis J Giles
Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661778/immunogenomic-analyses-of-advanced-serous-ovarian-cancer-reveal-immune-score-is-a-strong-prognostic-factor-and-an-indicator-of-chemo-sensitivity
#4
Li-Jun Di, Dapeng Hao, Jie Liu, Meng Chen, Jingjing Li, Li Wang, Guangyu Wang, Qi Zhao
PURPOSE: Ovarian cancer is one of the first human cancers for which in situ immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required. EXPERIMENTAL DESIGN: From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29628290/the-immune-landscape-of-cancer
#5
Vésteinn Thorsson, David L Gibbs, Scott D Brown, Denise Wolf, Dante S Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F Gao, Christopher L Plaisier, James A Eddy, Elad Ziv, Aedin C Culhane, Evan O Paull, I K Ashok Sivakumar, Andrew J Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S Parker, Lisle E Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M Reynolds, Reanne Bowlby, Andrea Califano, Andrew D Cherniack, Dimitris Anastassiou, Davide Bedognetti, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K Choueiri, John N Weinstein, Justin Guinney, Joel Saltz, Robert A Holt, Charles E Rabkin, Alexander J Lazar, Jonathan S Serody, Elizabeth G Demicco, Mary L Disis, Benjamin G Vincent, Llya Shmulevich
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis...
April 4, 2018: Immunity
https://www.readbyqxmd.com/read/29423108/cancer-immunogenomic-approach-to-neoantigen-discovery-in-a-checkpoint-blockade-responsive-murine-model-of-oral-cavity-squamous-cell-carcinoma
#6
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29357011/immunogenomics-a-negative-prostate-cancer-outcome-associated-with-tcr-%C3%AE-%C3%AE-recombinations
#7
Yaping N Tu, Wei Lue Tong, John M Yavorski, George Blanck
We developed a scripted algorithm, based on previous, earlier editions of the algorithm, to mine prostate cancer exome files for T-cell receptor (TcR) recombination reads: Reads representing TcR gene recombinations were identified in 497 prostate cancer exome files from the cancer genome atlas (TCGA). As has been reported for melanoma, co-detection of productive TcR-α and TcR-β recombination reads correlated with an RNA expression signature representing T-cell exhaustion, particularly with high RNA levels for PD-1 and PD-L1, in comparison to several different control sets of samples...
January 22, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/29315503/the-clinical-implications-of-immunogenomics-in-colorectal-cancer-a-path-for-precision-medicine
#8
REVIEW
Jenny M Riley, Ashley W Cross, Chrystal M Paulos, Mark P Rubinstein, John Wrangle, E Ramsay Camp
Colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths in the United States. Large multi-omic databases, such as The Cancer Genome Atlas and the International Colorectal Cancer Subtyping Consortium, have identified distinct molecular subtypes related to anatomy. The identification of genomic alterations in CRC is now critical because of the recent success and US Food and Drug Administration approval of pembrolizumab and nivolumab for microsatellite-instable tumors...
April 15, 2018: Cancer
https://www.readbyqxmd.com/read/29296203/the-pathogenesis-of-diclofenac-induced-immunoallergic-hepatitis-in-a-canine-model-of-liver-injury
#9
Saravanakumar Selvaraj, Jung-Hwa Oh, Reinhard Spanel, Florian Länger, Hyoung-Yun Han, Eun-Hee Lee, Seokjoo Yoon, Jürgen Borlak
Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130882/simultaneous-enumeration-of-cancer-and-immune-cell-types-from-bulk-tumor-gene-expression-data
#10
Julien Racle, Kaat de Jonge, Petra Baumgaertner, Daniel E Speiser, David Gfeller
Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens...
November 13, 2017: ELife
https://www.readbyqxmd.com/read/29064420/immunogenomic-classification-of-colorectal-cancer-and-therapeutic-implications
#11
REVIEW
Jessica Roelands, Peter J K Kuppen, Louis Vermeulen, Cristina Maccalli, Julie Decock, Ena Wang, Francesco M Marincola, Davide Bedognetti, Wouter Hendrickx
The immune system has a substantial effect on colorectal cancer (CRC) progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies) is influenced by the immune system. The molecular characterization of colorectal cancer (CRC) has led to the identification of favorable and unfavorable immunological attributes linked to clinical outcome. With the definition of consensus molecular subtypes (CMSs) based on transcriptomic profiles, multiple characteristics have been proposed to be responsible for the development of the tumor immune microenvironment and corresponding mechanisms of immune escape...
October 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28978691/reconstructing-antibody-repertoires-from-error-prone-immunosequencing-reads
#12
Alexander Shlemov, Sergey Bankevich, Andrey Bzikadze, Maria A Turchaninova, Yana Safonova, Pavel A Pevzner
Transforming error-prone immunosequencing datasets into Ab repertoires is a fundamental problem in immunogenomics, and a prerequisite for studies of immune responses. Although various repertoire reconstruction algorithms were released in the last 3 y, it remains unclear how to benchmark them and how to assess the accuracy of the reconstructed repertoires. We describe an accurate IgReC algorithm for constructing Ab repertoires from high-throughput immunosequencing datasets and a new framework for assessing the quality of reconstructed repertoires...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28924003/learning-the-high-dimensional-immunogenomic-features-that-predict-public-and-private-antibody-repertoires
#13
Victor Greiff, Cédric R Weber, Johannes Palme, Ulrich Bodenhofer, Enkelejda Miho, Ulrike Menzel, Sai T Reddy
Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone-specific immunogenomic differences concentrated in CDR3's N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28899059/targeting-neoantigens-in-glioblastoma-an-overview-of-cancer-immunogenomics-and-translational-implications
#14
Tanner M Johanns, Jay A Bowman-Kirigin, Connor Liu, Gavin P Dunn
No abstract text is available yet for this article.
September 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28841418/heterogeneous-tumor-immune-microenvironments-among-differentially-growing-metastases-in-an-ovarian-cancer-patient
#15
Alejandro Jiménez-Sánchez, Danish Memon, Stephane Pourpe, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B Gill, Kay J Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Tyler Walther, Carol Aghajanian, Jedd D Wolchok, Evis Sala, Taha Merghoub, Alexandra Snyder, Martin L Miller
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28754634/an-androgen-regulated-mir-2909-modulates-tgf%C3%AE-signalling-through-ar-mir-2909-axis-in-prostate-cancer
#16
Shiekh Gazalla Ayub, Deepak Kaul, Taha Ayub
In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate immunogenomics and oncogenomics. The present study investigated the role of miR-2909 in the pathogenesis of PCa and the potential signalling pathways through which it operates. We have identified miR-2909 as a novel mediator of androgen/androgen receptor (AR) signalling that enhances the proliferation potential of PCa cells and assists in cancer survival under reduced androgen levels...
October 5, 2017: Gene
https://www.readbyqxmd.com/read/28751445/head-and-neck-carcinoma-immunotherapy-facts-and-hopes
#17
REVIEW
Theresa L Whiteside
Cancer of the head and neck (HNC) is a heterogeneous disease of the upper aerodigestive tract, encompassing distinct histologic types, different anatomic sites, and human papillomavirus (HPV)-positive as well as HPV-negative cancers. Advanced/recurrent HNCs have poor prognosis with low survival rates. Tumor-mediated inhibition of antitumor immune responses and a high mutational burden are common features of HNCs. Both are responsible for the successful escape of these tumors from the host immune system. HNCs evolve numerous mechanisms of evasion from immune destruction...
January 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28718505/immunogenomic-approaches-to-understand-the-function-of-immune-disease-variants
#18
REVIEW
Dafni A Glinos, Blagoje Soskic, Gosia Trynka
Mapping hundreds of genetic variants through genome wide association studies provided an opportunity to gain insights into the pathobiology of immune-mediated diseases. However, as most of the disease variants fall outside the gene coding sequences the functional interpretation of the exact role of the associated variants remains to be determined. The integration of disease-associated variants with large scale genomic maps of cell-type-specific gene regulation at both chromatin and transcript levels deliver examples of functionally prioritized causal variants and genes...
December 2017: Immunology
https://www.readbyqxmd.com/read/28633385/timiner-ngs-data-mining-pipeline-for-cancer-immunology-and-immunotherapy
#19
Elias Tappeiner, Francesca Finotello, Pornpimol Charoentong, Clemens Mayer, Dietmar Rieder, Zlatko Trajanoski
Summary: Recently, a number of powerful computational tools for dissecting tumor-immune cell interactions from next-generation sequencing data have been developed. However, the assembly of analytical pipelines and execution of multi-step workflows are laborious and involve a large number of intermediate steps with many dependencies and parameter settings. Here we present TIminer, an easy-to-use computational pipeline for mining tumor-immune cell interactions from next-generation sequencing data...
October 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#20
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
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