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  1. Article ; Online: Prediction of neoepitopes from murine sequencing data.

    Bjerregaard, Anne-Mette / Pedersen, Thomas Kainamura / Marquard, Andrea Marion / Hadrup, Sine Reker

    Cancer immunology, immunotherapy : CII

    2018  Volume 68, Issue 1, Page(s) 159–161

    MeSH term(s) Animals ; Cell Line, Tumor ; Computational Biology/methods ; Epitopes, T-Lymphocyte/immunology ; High-Throughput Nucleotide Sequencing/methods ; Immunotherapy/methods ; Internet ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/therapy ; Software
    Chemical Substances Epitopes, T-Lymphocyte
    Language English
    Publishing date 2018-10-05
    Publishing country Germany
    Document type Letter
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-018-2254-5
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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Tumor-Infiltrating T Cells From Clear Cell Renal Cell Carcinoma Patients Recognize Neoepitopes Derived From Point and Frameshift Mutations.

    Hansen, Ulla Kring / Ramskov, Sofie / Bjerregaard, Anne-Mette / Borch, Annie / Andersen, Rikke / Draghi, Arianna / Donia, Marco / Bentzen, Amalie Kai / Marquard, Andrea Marion / Szallasi, Zoltan / Eklund, Aron Charles / Svane, Inge Marie / Hadrup, Sine Reker

    Frontiers in immunology

    2020  Volume 11, Page(s) 373

    Abstract: Mutation-derived neoantigens are important targets for T cell-mediated reactivity toward tumors and, due to their unique tumor expression, an attractive target for immunotherapy. Neoepitope-specific T cells have been detected across a number of solid ... ...

    Abstract Mutation-derived neoantigens are important targets for T cell-mediated reactivity toward tumors and, due to their unique tumor expression, an attractive target for immunotherapy. Neoepitope-specific T cells have been detected across a number of solid cancers with high mutational burden tumors, but neoepitopes have been mostly selected from single nucleotide variations (SNVs), and little focus has been given to neoepitopes derived from in-frame and frameshift indels, which might be equally important and potentially highly immunogenic. Clear cell renal cell carcinomas (ccRCCs) are medium-range mutational burden tumors with a high pan-cancer proportion of frameshift mutations. In this study, the mutational landscape of tumors from six RCC patients was analyzed by whole-exome sequencing (WES) of DNA from tumor fragments (TFs), autologous tumor cell lines (TCLs), and tumor-infiltrating lymphocytes (TILs, germline reference). Neopeptides were predicted using MuPeXI, and patient-specific peptide-MHC (pMHC) libraries were created for all neopeptides with a rank score < 2 for binding to the patient's HLAs. T cell recognition toward neoepitopes in TILs was evaluated using the
    MeSH term(s) Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/immunology ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Frameshift Mutation ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Point Mutation ; T-Lymphocytes/immunology
    Chemical Substances Antigens, Neoplasm ; Epitopes, T-Lymphocyte
    Language English
    Publishing date 2020-03-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00373
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  3. Article ; Online: CD8

    Pedersen, Natasja Wulff / Holm, Anja / Kristensen, Nikolaj Pagh / Bjerregaard, Anne-Mette / Bentzen, Amalie Kai / Marquard, Andrea Marion / Tamhane, Tripti / Burgdorf, Kristoffer Sølvsten / Ullum, Henrik / Jennum, Poul / Knudsen, Stine / Hadrup, Sine Reker / Kornum, Birgitte Rahbek

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 837

    Abstract: Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease ... ...

    Abstract Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4
    MeSH term(s) Adolescent ; Adult ; CD8-Positive T-Lymphocytes/immunology ; Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; HLA-DQ beta-Chains/genetics ; Humans ; Male ; Middle Aged ; Narcolepsy/genetics ; Narcolepsy/immunology ; Neurons/metabolism ; Orexins/immunology ; Orexins/metabolism ; Peptides/immunology
    Chemical Substances HLA-DQ beta-Chains ; HLA-DQB1 antigen ; Orexins ; Peptides
    Language English
    Publishing date 2019-02-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-08774-1
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  4. Article ; Online: CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens

    Natasja Wulff Pedersen / Anja Holm / Nikolaj Pagh Kristensen / Anne-Mette Bjerregaard / Amalie Kai Bentzen / Andrea Marion Marquard / Tripti Tamhane / Kristoffer Sølvsten Burgdorf / Henrik Ullum / Poul Jennum / Stine Knudsen / Sine Reker Hadrup / Birgitte Rahbek Kornum

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of ... ...

    Abstract Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.
    Keywords Science ; Q
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens

    Natasja Wulff Pedersen / Anja Holm / Nikolaj Pagh Kristensen / Anne-Mette Bjerregaard / Amalie Kai Bentzen / Andrea Marion Marquard / Tripti Tamhane / Kristoffer Sølvsten Burgdorf / Henrik Ullum / Poul Jennum / Stine Knudsen / Sine Reker Hadrup / Birgitte Rahbek Kornum

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of ... ...

    Abstract Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.
    Keywords Science ; Q
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers.

    Saini, Sunil Kumar / Ørskov, Andreas Due / Bjerregaard, Anne-Mette / Unnikrishnan, Ashwin / Holmberg-Thydén, Staffan / Borch, Annie / Jensen, Kathrine Valentini / Anande, Govardhan / Bentzen, Amalie Kai / Marquard, Andrea Marion / Tamhane, Tripti / Treppendahl, Marianne Bach / Gang, Anne Ortved / Dufva, Inge Høgh / Szallasi, Zoltan / Ternette, Nicola / Pedersen, Anders Gorm / Eklund, Aron Charles / Pimanda, John /
    Grønbæk, Kirsten / Hadrup, Sine Reker

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 5660

    Abstract: Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, ...

    Abstract Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, we evaluate the potential for T cell recognition of HERV elements in myeloid malignancies by mapping transcribed HERV genes and generating a library of 1169 potential antigenic HERV-derived peptides predicted for presentation by 4 HLA class I molecules. Using DNA barcode-labeled MHC-I multimers, we find CD8
    MeSH term(s) CD8-Positive T-Lymphocytes ; Endogenous Retroviruses/genetics ; Epigenesis, Genetic ; Epitopes, T-Lymphocyte ; Gene Expression Profiling ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/therapy ; Hematologic Neoplasms/virology ; Humans ; Immunotherapy ; Monitoring, Immunologic ; Myeloid Cells ; Neoplasms ; T-Lymphocytes/metabolism ; T-Lymphocytes/virology
    Chemical Substances Epitopes, T-Lymphocyte
    Language English
    Publishing date 2020-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-19464-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

    Sunil Kumar Saini / Andreas Due Ørskov / Anne-Mette Bjerregaard / Ashwin Unnikrishnan / Staffan Holmberg-Thydén / Annie Borch / Kathrine Valentini Jensen / Govardhan Anande / Amalie Kai Bentzen / Andrea Marion Marquard / Tripti Tamhane / Marianne Bach Treppendahl / Anne Ortved Gang / Inge Høgh Dufva / Zoltan Szallasi / Nicola Ternette / Anders Gorm Pedersen / Aron Charles Eklund / John Pimanda /
    Kirsten Grønbæk / Sine Reker Hadrup

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell ... ...

    Abstract Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell recognition in myeloid cancer patients to implicate HERVs as potential therapeutic targets.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

    Sunil Kumar Saini / Andreas Due Ørskov / Anne-Mette Bjerregaard / Ashwin Unnikrishnan / Staffan Holmberg-Thydén / Annie Borch / Kathrine Valentini Jensen / Govardhan Anande / Amalie Kai Bentzen / Andrea Marion Marquard / Tripti Tamhane / Marianne Bach Treppendahl / Anne Ortved Gang / Inge Høgh Dufva / Zoltan Szallasi / Nicola Ternette / Anders Gorm Pedersen / Aron Charles Eklund / John Pimanda /
    Kirsten Grønbæk / Sine Reker Hadrup

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell ... ...

    Abstract Human endogenous retroviruses (HERV) normally remain quiescent, but can be reactivated by malignant transformation. Here the authors find, via HERV peptide library testing and tetramer validation, more profound HERV transcription and associated T cell recognition in myeloid cancer patients to implicate HERVs as potential therapeutic targets.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: TumorTracer: a method to identify the tissue of origin from the somatic mutations of a tumor specimen.

    Marquard, Andrea Marion / Birkbak, Nicolai Juul / Thomas, Cecilia Engel / Favero, Francesco / Krzystanek, Marcin / Lefebvre, Celine / Ferté, Charles / Jamal-Hanjani, Mariam / Wilson, Gareth A / Shafi, Seema / Swanton, Charles / André, Fabrice / Szallasi, Zoltan / Eklund, Aron Charles

    BMC medical genomics

    2015  Volume 8, Page(s) 58

    Abstract: Background: A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been ... ...

    Abstract Background: A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been previously demonstrated that the somatic point mutations detected in a tumor can be used to identify its site of origin with limited accuracy. We hypothesized that higher accuracy could be achieved by a classification algorithm based on the following feature sets: 1) the number of nonsynonymous point mutations in a set of 232 specific cancer-associated genes, 2) frequencies of the 96 classes of single-nucleotide substitution determined by the flanking bases, and 3) copy number profiles, if available.
    Methods: We used publicly available somatic mutation data from the COSMIC database to train random forest classifiers to distinguish among those tissues of origin for which sufficient data was available. We selected feature sets using cross-validation and then derived two final classifiers (with or without copy number profiles) using 80 % of the available tumors. We evaluated the accuracy using the remaining 20 %. For further validation, we assessed accuracy of the without-copy-number classifier on three independent data sets: 1669 newly available public tumors of various types, a cohort of 91 breast metastases, and a set of 24 specimens from 9 lung cancer patients subjected to multiregion sequencing.
    Results: The cross-validation accuracy was highest when all three types of information were used. On the left-out COSMIC data not used for training, we achieved a classification accuracy of 85 % across 6 primary sites (with copy numbers), and 69 % across 10 primary sites (without copy numbers). Importantly, a derived confidence score could distinguish tumors that could be identified with 95 % accuracy (32 %/75 % of tumors with/without copy numbers) from those that were less certain. Accuracy in the independent data sets was 46 %, 53 % and 89 % respectively, similar to the accuracy expected from the training data.
    Conclusions: Identification of primary site from point mutation and/or copy number data may be accurate enough to aid clinical diagnosis of cancers of unknown primary origin.
    MeSH term(s) Breast Neoplasms/genetics ; Databases, Genetic ; Female ; Genes, Neoplasm ; Humans ; Lung Neoplasms/genetics ; Male ; Organ Specificity ; Point Mutation ; Polymorphism, Single Nucleotide
    Language English
    Publishing date 2015-10-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2411865-5
    ISSN 1755-8794 ; 1755-8794
    ISSN (online) 1755-8794
    ISSN 1755-8794
    DOI 10.1186/s12920-015-0130-0
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  10. Article ; Online: Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes.

    Bentzen, Amalie Kai / Marquard, Andrea Marion / Lyngaa, Rikke / Saini, Sunil Kumar / Ramskov, Sofie / Donia, Marco / Such, Lina / Furness, Andrew J S / McGranahan, Nicholas / Rosenthal, Rachel / Straten, Per Thor / Szallasi, Zoltan / Svane, Inge Marie / Swanton, Charles / Quezada, Sergio A / Jakobsen, Søren Nyboe / Eklund, Aron Charles / Hadrup, Sine Reker

    Nature biotechnology

    2016  Volume 34, Issue 10, Page(s) 1037–1045

    Abstract: Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in ... ...

    Abstract Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (MHC) multimers labeled with individual DNA barcodes to screen >1,000 peptide specificities in a single sample, and detect low-frequency CD8 T cells specific for virus- or cancer-restricted antigens. When analyzing T-cell recognition of shared melanoma antigens before and after adoptive cell therapy in melanoma patients, we observe a greater number of melanoma-specific T-cell populations compared with cytometry-based approaches. Furthermore, we detect neoepitope-specific T cells in tumor-infiltrating lymphocytes and peripheral blood from patients with non-small cell lung cancer. Barcode-labeled pMHC multimers enable the combination of functional T-cell analysis with large-scale epitope recognition profiling for the characterization of T-cell recognition in various diseases, including in small clinical samples.
    MeSH term(s) Antigens/genetics ; Antigens/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; DNA Barcoding, Taxonomic ; Genes, MHC Class I/genetics ; Genes, MHC Class I/immunology ; High-Throughput Screening Assays/methods ; Humans ; Immunoassay/methods ; Peptides/genetics ; Peptides/immunology ; Protein Multimerization/genetics ; Protein Multimerization/immunology ; Staining and Labeling/methods
    Chemical Substances Antigens ; Peptides
    Language English
    Publishing date 2016-08-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/nbt.3662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2167: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 137: Show issues
    Zs.MG 43: Show issues

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