• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2020
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2020
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Sphingosine Kinase Blockade Leads to Increased Natural Killer T Cell Responses to Mantle Cell Lymphoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Lee, M.S.
    Sun, W.
    Webb, T.J.
    Date
    2020
    Journal
    Cells
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/cells9041030
    Abstract
    Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma. Despite being responsive to combination chemotherapy, median survival remains around 5 years due to high rates of relapse. Sphingolipid metabolism regulates MCL survival and proliferation and we found that sphingosine-1-phosphate (S1P) is upregulated in MCL cells. Therapeutic targeting of the S1P1 receptor or knockdown of sphingosine kinase 1 (SK1), the enzyme responsible for generating S1P, in human MCL cells results in a significant increase in Natural Killer T (NKT) cell activation. NKT cells recognize glycolipid antigens presented on CD1d and can reduce MCL tumor burden in vivo. Lipidomic studies identified cardiolipin, which has been reported to bind to CD1d molecules, as being upregulated in SK1 knockdown cells. We found that the pretreatment of antigen presenting cells with cardiolipin leads to increased cytokine production by NKT cell hybridomas. Furthermore, the ability of cardiolipin to activate NKT cells was dependent on the structure of its acyl chains. Collectively, these studies delineate novel pathways important for immune recognition of malignant cells and could lead to the development of new treatments for lymphoma.
    Keyword
    cardiolipin
    Mantle cell lymphoma
    NKT cells
    sphingosine kinase
    sphingosine-1-phosphate
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084031103&doi=10.3390%2fcells9041030&partnerID=40&md5=89c4fa61d5d128bcee3d7284bf700392; http://hdl.handle.net/10713/12707
    ae974a485f413a2113503eed53cd6c53
    10.3390/cells9041030
    Scopus Count
    Collections
    UMB Open Access Articles 2020

    entitlement

    Related articles

    • TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: implications for inflammation in atherosclerosis.
    • Authors: Ito S, Iwaki S, Kondo R, Satoh M, Iwabuchi K, Ohkawa R, Mishima Y, Yatomi Y, Furumoto T, Tsutsui H, Fujii S
    • Issue date: 2014 Jun
    • Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to lymphoma.
    • Authors: Tiper IV, Webb TJ
    • Issue date: 2016 Nov
    • FTY720, a sphingosine 1-phosphate receptor modulator, inhibits CD1d-restricted NKT cells by suppressing cytokine production but not migration.
    • Authors: Hwang SJ, Kim JH, Kim HY, Kim S, Chung DH
    • Issue date: 2010 Jan
    • Structural basis of NKT cell inhibition using the T-cell receptor-blocking anti-CD1d antibody 1B1.
    • Authors: Ying G, Wang J, Mallevaey T, Van Calenbergh S, Zajonc DM
    • Issue date: 2019 Aug 30
    • Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.
    • Authors: Webb TJ, Carey GB, East JE, Sun W, Bollino DR, Kimball AS, Brutkiewicz RR
    • Issue date: 2016 Aug
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.