{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:01:44Z","timestamp":1792440104116,"version":"4.5.0"},"reference-count":49,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949"],"award-info":[{"award-number":["GRK1949"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2098"],"award-info":[{"award-number":["GRK2098"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,11,15]]},"abstract":"<jats:p>\n                    Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes. However, the impact of cell-intrinsic ceramide on T cell function is not well characterized. By using T cell-specific Asm- or Ac-deficient mice, with reduced or elevated ceramide levels in T cells, we identified ceramide to play a crucial role in T cell function in vitro and in vivo. T cell-specific ablation of Asm in\n                    <jats:italic>\n                      Smpd1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      \/Cd4\n                      <jats:sup>cre\/+<\/jats:sup>\n                    <\/jats:italic>\n                    (Asm\/CD4cre) mice resulted in enhanced tumor progression associated with impaired T cell responses, whereas\n                    <jats:italic>\n                      Asah1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      \/Cd4\n                      <jats:sup>cre\/+<\/jats:sup>\n                    <\/jats:italic>\n                    (Ac\/CD4cre) mice showed reduced tumor growth rates and elevated T cell activation compared to the respective controls upon tumor transplantation. Further in vitro analysis revealed that decreased ceramide content supports CD4\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cell differentiation and interferes with cytotoxic activity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. In contrast, elevated ceramide concentration in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from Ac\/CD4cre mice was associated with enhanced cytotoxic activity. Strikingly, ceramide co-localized with the T cell receptor (TCR) and CD3 in the membrane of stimulated T cells and phosphorylation of TCR signaling molecules was elevated in Ac-deficient T cells. Hence, our results indicate that modulation of ceramide levels, by interfering with the Asm or Ac activity has an effect on T cell differentiation and function and might therefore represent a novel therapeutic strategy for the treatment of T cell-dependent diseases such as tumorigenesis.\n                  <\/jats:p>","DOI":"10.7554\/elife.83073","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T07:15:12Z","timestamp":1668496512000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.83073","source":"Crossref","is-referenced-by-count":35,"title":["Cell-intrinsic ceramides determine T cell function during melanoma progression"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-5591","authenticated-orcid":true,"given":"Matthias","family":"Hose","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"G\u00fcnther","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyad","family":"Naser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Biology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-3275","authenticated-orcid":true,"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Sch\u00f6nberger","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Physiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Falkenstein","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-4242","authenticated-orcid":true,"given":"Athanasios","family":"Papadamakis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin Anne","family":"Becker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Biology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Biology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4884-0581","authenticated-orcid":true,"given":"Adriana","family":"Haimovitz-Friedman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center","place":["New York City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-1698","authenticated-orcid":true,"given":"Jan","family":"Buer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-2892","authenticated-orcid":true,"given":"Astrid M","family":"Westendorf","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-0886","authenticated-orcid":true,"given":"Wiebke","family":"Hansen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mz5ra38","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1002\/eji.201445058","article-title":"Treg-cell depletion promotes chemokine production and accumulation of CXCR3 (+) conventional T cells in intestinal tumors","volume":"45","author":"Akeus","year":"2015","journal-title":"European Journal of Immunology"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0620-6","article-title":"Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy","volume":"16","author":"Angelova","year":"2015","journal-title":"Genome Biology"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.178","article-title":"Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses","volume":"6","author":"Bai","year":"2015","journal-title":"Cell Death & Disease"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"10922","DOI":"10.1074\/jbc.M610157200","article-title":"Alterations of ceramide\/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells","volume":"282","author":"Baran","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4049\/jimmunol.171.1.27","article-title":"Cutting edge: rapid in vivo killing by memory CD8 T cells","volume":"171","author":"Barber","year":"2003","journal-title":"Journal of Immunology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2014.00331","article-title":"Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons","volume":"5","author":"Beckmann","year":"2014","journal-title":"Frontiers in Physiology"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00815","article-title":"The neutral sphingomyelinase 2 is required to polarize and sustain T cell receptor signaling","volume":"9","author":"B\u00f6rtlein","year":"2018","journal-title":"Frontiers in Immunology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/eji.200324799","article-title":"Neuropilin-1: a surface marker of regulatory T cells","volume":"34","author":"Bruder","year":"2004","journal-title":"European Journal of Immunology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1016\/j.celrep.2019.07.044","article-title":"Pro-Survival lipid sphingosine-1-phosphate metabolically programs T cells to limit anti-tumor activity","volume":"28","author":"Chakraborty","year":"2019","journal-title":"Cell Reports"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/laban.254","article-title":"Estimation of rat mammary tumor volume using caliper and ultrasonography measurements","volume":"42","author":"Faustino-Rocha","year":"2013","journal-title":"Lab Animal"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s10549-011-1768-8","article-title":"C6-Ceramide and targeted inhibition of acid ceramidase induce synergistic decreases in breast cancer cell growth","volume":"133","author":"Flowers","year":"2012","journal-title":"Breast Cancer Research and Treatment"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1200\/JCO.2006.09.4565","article-title":"Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection","volume":"25","author":"Gao","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1126\/science.1082504","article-title":"Tumor response to radiotherapy regulated by endothelial cell apoptosis","volume":"300","author":"Garcia-Barros","year":"2003","journal-title":"Science"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"8285","DOI":"10.1158\/0008-5472.CAN-04-2715","article-title":"Host acid sphingomyelinase regulates microvascular function not tumor immunity","volume":"64","author":"Garcia-Barros","year":"2004","journal-title":"CANCER Research"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s00262-020-02492-0","article-title":"Pkc\u03b6 mediated anti-proliferative effect of C2 ceramide on neutralization of the tumor microenvironment and melanoma regression","volume":"69","author":"Ghosh","year":"2020","journal-title":"Cancer Immunology, Immunotherapy"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.critrevonc.2019.03.018","article-title":"Sphingolipids and acid ceramidase as therapeutic targets in cancer therapy","volume":"138","author":"Govindarajah","year":"2019","journal-title":"Critical Reviews in Oncology\/Hematology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"5457","DOI":"10.1038\/sj.onc.1206540","article-title":"Ceramide-mediated clustering is required for CD95-DISC formation","volume":"22","author":"Grassm\u00e9","year":"2003","journal-title":"Oncogene"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/nm.3214","article-title":"Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs","volume":"19","author":"Gulbins","year":"2013","journal-title":"Nature Medicine"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1038\/s41380-018-0090-9","article-title":"Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide","volume":"23","author":"Gulbins","year":"2018","journal-title":"Molecular Psychiatry"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1084\/jem.20111497","article-title":"Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth","volume":"209","author":"Hansen","year":"2012","journal-title":"The Journal of Experimental Medicine"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ni.1757","article-title":"Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes","volume":"10","author":"Herz","year":"2009","journal-title":"Nature Immunology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","article-title":"T cell receptor antagonist peptides induce positive selection","volume":"76","author":"Hogquist","year":"1994","journal-title":"Cell"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"3130","DOI":"10.4049\/jimmunol.1600691","article-title":"Inhibition of acid sphingomyelinase allows for selective targeting of CD4+ conventional versus foxp3+ regulatory T cells","volume":"197","author":"Hollmann","year":"2016","journal-title":"Journal of Immunology"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/ng0795-288","article-title":"Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease","volume":"10","author":"Horinouchi","year":"1995","journal-title":"Nature Genetics"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01225","article-title":"T cell-specific overexpression of acid sphingomyelinase results in elevated T cell activation and reduced parasitemia during Plasmodium yoelii infection","volume":"10","author":"Hose","year":"2019","journal-title":"Frontiers in Immunology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1016\/S1470-2045(11)70155-3","article-title":"Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy?","volume":"13","author":"Jacobs","year":"2012","journal-title":"The Lancet. Oncology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"896","DOI":"10.4049\/jimmunol.177.2.896","article-title":"Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells","volume":"177","author":"Jarnicki","year":"2006","journal-title":"Journal of Immunology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/1097-4652(200009)184:3<285::AID-JCP2>3.0.CO;2-3","article-title":"Compartmentalization of ceramide signaling: physical foundations and biological effects","volume":"184","author":"Kolesnick","year":"2000","journal-title":"Journal of Cellular Physiology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1007\/s00702-005-0374-5","article-title":"High activity of acid sphingomyelinase in major depression","volume":"112","author":"Kornhuber","year":"2005","journal-title":"Journal of Neural Transmission"},{"key":"bib31","first-page":"1","article-title":"Protein measurement byt the folin reagent","volume":"1","author":"Lowry","year":"1951","journal-title":"The Journal of Biological Chemistry"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10215029","article-title":"Prevalence of cancer in acid sphingomyelinase deficiency","volume":"10","author":"Mauhin","year":"2021","journal-title":"Journal of Clinical Medicine"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1285","article-title":"Unidirectional transfer of microrna-loaded exosomes from T cells to antigen-presenting cells","volume":"2","author":"Mittelbrunn","year":"2011","journal-title":"Nature Communications"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nrc3398","article-title":"Ceramide-orchestrated signalling in cancer cells","volume":"13","author":"Morad","year":"2013","journal-title":"Nature Reviews. Cancer"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004574","article-title":"Neutral sphingomyelinase in physiological and measles virus induced T cell suppression","volume":"10","author":"Mueller","year":"2014","journal-title":"PLOS Pathogens"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1194\/jlr.RA120000682","article-title":"Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro","volume":"61","author":"Naser","year":"2020","journal-title":"Journal of Lipid Research"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/nrc1411","article-title":"Biologically active sphingolipids in cancer pathogenesis and treatment","volume":"4","author":"Ogretmen","year":"2004","journal-title":"Nature Reviews. Cancer"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"3014","DOI":"10.1007\/978-3-540-29676-8_1286","article-title":"Niemann-Pick disease types A and B","volume":"53","author":"Ohno","year":"1995","journal-title":"Nihon Rinsho. Japanese Journal of Clinical Medicine"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"5461","DOI":"10.1172\/JCI136928","article-title":"S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion","volume":"130","author":"Olesch","year":"2020","journal-title":"The Journal of Clinical Investigation"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"4258","DOI":"10.1158\/0008-5472.CAN-13-3065","article-title":"Transient ablation of regulatory T cells improves antitumor immunity in colitis-associated colon cancer","volume":"74","author":"Pastille","year":"2014","journal-title":"Cancer Research"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1093\/jjco\/hyi147","article-title":"An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer","volume":"35","author":"Sakamoto","year":"2005","journal-title":"Japanese Journal of Clinical Oncology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/s0092-8674(00)80091-4","article-title":"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis","volume":"86","author":"Santana","year":"1996","journal-title":"Cell"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"18538","DOI":"10.1073\/pnas.0509182102","article-title":"Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+\/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer","volume":"102","author":"Sato","year":"2005","journal-title":"PNAS"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.beem.2014.10.002","article-title":"Types A and B Niemann-Pick disease","volume":"29","author":"Schuchman","year":"2015","journal-title":"Best Practice & Research. Clinical Endocrinology & Metabolism"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1158\/2326-6066.CIR-14-0190","article-title":"Robust antitumor effects of combined anti-CD4-depleting antibody and anti-PD-1\/PD-L1 immune checkpoint antibody treatment in mice","volume":"3","author":"Ueha","year":"2015","journal-title":"Cancer Immunology Research"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab020","article-title":"Inhibition of acid sphingomyelinase increases regulatory T cells in humans","volume":"3","author":"Wiese","year":"2021","journal-title":"Brain Communications"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0845-z","article-title":"Acid ceramidase deficiency: farber disease and SMA-PME","volume":"13","author":"Yu","year":"2018","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.bbamem.2008.07.030","article-title":"Ceramide-Enriched membrane domains -- structure and function","volume":"1788","author":"Zhang","year":"2009","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1159\/000447806","article-title":"Acid sphingomyelinase (ASM) is a negative regulator of regulatory T cell (Treg) development","volume":"39","author":"Zhou","year":"2016","journal-title":"Cellular Physiology and Biochemistry"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83073\/elife-83073-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83073\/elife-83073-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/83073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:26:45Z","timestamp":1697059605000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/83073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,25]]},"references-count":49,"alternative-id":["10.7554\/eLife.83073"],"URL":"https:\/\/doi.org\/10.7554\/elife.83073","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.08.31.505996","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.83073.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83073.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83073.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,25]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e83073"}}