{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:08:08Z","timestamp":1790770088076,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA162277"],"award-info":[{"award-number":["CA162277"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA199544"],"award-info":[{"award-number":["CA199544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA184469"],"award-info":[{"award-number":["CA184469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin\u2019s 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.<\/jats:p>","DOI":"10.3390\/cells9041030","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T04:15:13Z","timestamp":1587528913000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sphingosine Kinase Blockade Leads to Increased Natural Killer T Cell Responses to Mantle Cell Lymphoma"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8652-2093","authenticated-orcid":false,"given":"Michael S.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-1804","authenticated-orcid":false,"given":"Wenji","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3086-6414","authenticated-orcid":false,"given":"Tonya J.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1182\/blood-2010-04-189977","article-title":"Mantle cell lymphoma: Biology, pathogenesis, and the molecular basis of treatment in the genomic era","volume":"117","author":"Dreyling","year":"2011","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.18632\/oncotarget.426","article-title":"Novel targeted therapies for mantle cell lymphoma","volume":"3","author":"Alinari","year":"2012","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.12688\/f1000research.14122.1","article-title":"Current overview and treatment of mantle cell lymphoma","volume":"7","author":"Schieber","year":"2018","journal-title":"F1000Research"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1182\/blood-2016-11-751065","article-title":"Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis","volume":"129","author":"Gorini","year":"2017","journal-title":"Blood"},{"key":"ref_5","first-page":"5102","article-title":"Antitumor Cytotoxicity Mediated by Ligand-activated Human Va24 NKT Cells","volume":"59","author":"Kawano","year":"1999","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0065-230X(08)00408-9","article-title":"The Role of NKT Cells in Tumor Immunity","volume":"101","author":"Terabe","year":"2008","journal-title":"Adv. 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