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Immunogenomics

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https://www.readbyqxmd.com/read/28633385/timiner-ngs-data-mining-pipeline-for-cancer-immunology-and-immunotherapy
#1
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 (NGS) 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 NGS data. TIminer enables integrative immunogenomic analyses, including: human leukocyte antigens typing, neoantigen prediction, characterization of immune infiltrates, and quantification of tumor immunogenicity...
June 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#2
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
https://www.readbyqxmd.com/read/28507796/lyg1-exerts-antitumor-function-through-promoting-the-activation-proliferation-and-function-of-cd4-t-cells
#3
Huihui Liu, Yanfei Zhang, Zhengyang Liu, Pingzhang Wang, Xiaoning Mo, Weiwei Fu, Wanchang Liu, Yingying Cheng, Wenling Han
Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1(-/-) mice, CD4(+)- or CD8(+) T cell-deleted mice. It could increase the number of CD4(+) and CD8(+) T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNγ production by T cells in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28410300/applied-cancer-immunogenomics-leveraging-neoantigen-discovery-in-glioblastoma
#4
REVIEW
Tanner M Johanns, Gavin P Dunn
Glioblastoma (GBM) remains a significant cause of cancer-related mortality in pediatric and adult patients with limited treatment options. Immunotherapy represents a promising new therapeutic approach in many solid and hematologic malignancies, including GBM, although only a subset of patients responds clinically. Thus, current efforts are focused on identifying patients most likely to benefit from immune-based therapies. The cancer immunogenomics approach identifies candidate neoantigens from genomics information and represents a potentially exciting new space in precision neuro-oncology...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#5
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28389595/cancer-immunogenomics-computational-neoantigen-identification-and-vaccine-design
#6
Jasreet Hundal, Christopher A Miller, Malachi Griffith, Obi L Griffith, Jason Walker, Susanna Kiwala, Aaron Graubert, Joshua McMichael, Adam Coffman, Elaine R Mardis
The application of modern high-throughput genomics to the study of cancer genomes has exploded in the past few years, yielding unanticipated insights into the myriad and complex combinations of genomic alterations that lead to the development of cancers. Coincident with these genomic approaches have been computational analyses that are capable of multiplex evaluations of genomic data toward specific therapeutic end points. One such approach is called "immunogenomics" and is now being developed to interpret protein-altering changes in cancer cells in the context of predicted preferential binding of these altered peptides by the patient's immune molecules, specifically human leukocyte antigen (HLA) class I and II proteins...
April 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28374766/reprogramming-mhc-specificity-by-crispr-cas9-assisted-cassette-exchange
#7
William Kelton, Ann Cathrin Waindok, Theresa Pesch, Mark Pogson, Kyle Ford, Cristina Parola, Sai T Reddy
The development of programmable nucleases has enabled the application of new genome engineering strategies for cellular immunotherapy. While targeted nucleases have mostly been used to knock-out or knock-in genes in immune cells, the scarless exchange of entire immunogenomic alleles would be of great interest. In particular, reprogramming the polymorphic MHC locus could enable the creation of matched donors for allogeneic cellular transplantation. Here we show a proof-of-concept for reprogramming MHC-specificity by performing CRISPR-Cas9-assisted cassette exchange...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322934/comparative-immunogenomics-of-molluscs
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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