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dc.contributor.authorLee, M.S.
dc.contributor.authorSun, W.
dc.contributor.authorWebb, T.J.
dc.date.accessioned2020-05-08T20:13:21Z
dc.date.available2020-05-08T20:13:21Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85084031103&doi=10.3390%2fcells9041030&partnerID=40&md5=89c4fa61d5d128bcee3d7284bf700392
dc.identifier.urihttp://hdl.handle.net/10713/12707
dc.description.abstractMantle 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.en_US
dc.description.urihttps://doi.org/10.3390/cells9041030en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCells
dc.subjectcardiolipinen_US
dc.subjectMantle cell lymphomaen_US
dc.subjectNKT cellsen_US
dc.subjectsphingosine kinaseen_US
dc.subjectsphingosine-1-phosphateen_US
dc.titleSphingosine Kinase Blockade Leads to Increased Natural Killer T Cell Responses to Mantle Cell Lymphomaen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cells9041030
dc.identifier.pmid32326225


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