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  1. Article ; Online: Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model.

    El Meskini, Rajaa / Atkinson, Devon / Kulaga, Alan / Abdelmaksoud, Abdalla / Gumprecht, Michelle / Pate, Nathan / Hayes, Susana / Oberst, Michael / Kaplan, Ian M / Raber, Patrick / Van Dyke, Terry / Sharan, Shyam K / Hollingsworth, Robert / Day, Chi-Ping / Merlino, Glenn / Weaver Ohler, Zoë

    Molecular cancer research : MCR

    2021  Volume 19, Issue 8, Page(s) 1422–1436

    Abstract: Only a subset of patients responds to immune checkpoint blockade (ICB) in melanoma. A preclinical model recapitulating the clinical activity of ICB would provide a valuable platform for mechanistic studies. We used melanoma tumors arising from an ... ...

    Abstract Only a subset of patients responds to immune checkpoint blockade (ICB) in melanoma. A preclinical model recapitulating the clinical activity of ICB would provide a valuable platform for mechanistic studies. We used melanoma tumors arising from an Hgf
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/metabolism ; Biomarkers/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Disease Models, Animal ; Melanoma/drug therapy ; Melanoma/metabolism ; Mice ; Receptors, Antigen, T-Cell/metabolism
    Chemical Substances Antibodies, Monoclonal ; B7-H1 Antigen ; Biomarkers ; Cd274 protein, mouse ; Receptors, Antigen, T-Cell ; durvalumab (28X28X9OKV)
    Language English
    Publishing date 2021-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-20-0881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5744: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Evaluation of ultra-low input RNA sequencing for the study of human T cell transcriptome.

    Wang, Jingya / Rieder, Sadiye Amcaoglu / Wu, Jincheng / Hayes, Susana / Halpin, Rebecca A / de Los Reyes, Melissa / Shrestha, Yashaswi / Kolbeck, Roland / Raja, Rajiv

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 8445

    Abstract: Deeper understanding of T cell biology is crucial for the development of new therapeutics. Human naïve T cells have low RNA content and their numbers can be limiting; therefore we set out to determine the parameters for robust ultra-low input RNA ... ...

    Abstract Deeper understanding of T cell biology is crucial for the development of new therapeutics. Human naïve T cells have low RNA content and their numbers can be limiting; therefore we set out to determine the parameters for robust ultra-low input RNA sequencing. We performed transcriptome profiling at different cell inputs and compared three protocols: Switching Mechanism at 5' End of RNA Template technology (SMART) with two different library preparation methods (Nextera and Clontech), and AmpliSeq technology. As the cell input decreased the number of detected coding genes decreased with SMART, while stayed constant with AmpliSeq. However, SMART enables detection of non-coding genes, which is not feasible for AmpliSeq. The detection is dependent on gene abundance, but not transcript length. The consistency between technical replicates and cell inputs was comparable across methods above 1 K but highly variable at 100 cell input. Sensitivity of detection for differentially expressed genes decreased dramatically with decreased cell inputs in all protocols, support that additional approaches, such as pathway enrichment, are important for data interpretation at ultra-low input. Finally, T cell activation signature was detected at 1 K cell input and above in all protocols, with AmpliSeq showing better detection at 100 cells.
    MeSH term(s) Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; RNA, Messenger/genetics ; Sequence Analysis, RNA/methods ; T-Lymphocytes/metabolism ; Transcriptome/genetics ; Whole Exome Sequencing
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2019-06-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-44902-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Distinct mechanisms govern populations of myeloid-derived suppressor cells in chronic viral infection and cancer.

    Tcyganov, Evgenii N / Hanabuchi, Shino / Hashimoto, Ayumi / Campbell, David / Kar, Gozde / Slidel, Timothy Wf / Cayatte, Corinne / Landry, Aimee / Pilataxi, Fernanda / Hayes, Susana / Dougherty, Brian / Hicks, Kristin C / Mulgrew, Kathy / Tang, Chih-Hang Anthony / Hu, Chih-Chi Andrew / Guo, Wei / Grivennikov, Sergei / Ali, Mohammed-Alkhatim A / Beltra, Jean-Christophe /
    Wherry, E John / Nefedova, Yulia / Gabrilovich, Dmitry I

    The Journal of clinical investigation

    2021  Volume 131, Issue 16

    Abstract: Myeloid-derived suppressor cells (MDSCs) are major negative regulators of immune responses in cancer and chronic infections. It remains unclear if regulation of MDSC activity in different conditions is controlled by similar mechanisms. We compared MDSCs ... ...

    Abstract Myeloid-derived suppressor cells (MDSCs) are major negative regulators of immune responses in cancer and chronic infections. It remains unclear if regulation of MDSC activity in different conditions is controlled by similar mechanisms. We compared MDSCs in mice with cancer and lymphocytic choriomeningitis virus (LCMV) infection. Chronic LCMV infection caused the development of monocytic MDSCs (M-MDSCs) but did not induce polymorphonuclear MDSCs (PMN-MDSCs). In contrast, both MDSC populations were present in cancer models. An acquisition of immune-suppressive activity by PMN-MDSCs in cancer was controlled by IRE1α and ATF6 pathways of the endoplasmic reticulum (ER) stress response. Abrogation of PMN-MDSC activity by blockade of the ER stress response resulted in an increase in tumor-specific immune response and reduced tumor progression. In contrast, the ER stress response was dispensable for suppressive activity of M-MDSCs in cancer and LCMV infection. Acquisition of immune-suppressive activity by M-MDSCs in spleens was mediated by IFN-γ signaling. However, it was dispensable for suppressive activity of M-MDSCs in tumor tissues. Suppressive activity of M-MDSCs in tumors was retained due to the effect of IL-6 present at high concentrations in the tumor site. These results demonstrate disease- and population-specific mechanisms of MDSC accumulation and the need for targeting different pathways to achieve inactivation of these cells.
    MeSH term(s) Animals ; Cell Line, Tumor ; Chronic Disease ; Endoplasmic Reticulum Stress/genetics ; Endoplasmic Reticulum Stress/immunology ; Female ; Humans ; Immune Tolerance/genetics ; Interferon-gamma/immunology ; Lymphocytic Choriomeningitis/genetics ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/classification ; Lymphocytic choriomeningitis virus/immunology ; Lymphocytic choriomeningitis virus/pathogenicity ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid-Derived Suppressor Cells/classification ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/metabolism ; Transcriptome ; Virus Diseases/genetics ; Virus Diseases/immunology ; Virus Diseases/metabolism
    Chemical Substances IFNG protein, mouse ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2021-07-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI145971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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