{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:13Z","timestamp":1787120833116,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013043","name":"Ariel University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Simvastatin (SIM), a member of the statin family, is commonly used to lower blood cholesterol levels, particularly low-density lipoprotein. Statins inhibit the action of hydroxy-methyl-glutaryl-coenzyme A reductase, an important enzyme in the synthesis of cholesterol and isoprenoids; they also have anti-inflammatory effects and can regulate membrane synthesis in cancer cells. Preliminary evidence suggests an association between SIM use and reduced cancer incidence. SIM\u2019s anti-cancer efficacy\n                      <jats:italic>in vivo<\/jats:italic>\n                      has been shown in studies on several solid tumors, but little is known about its effects on hematological cancers, such as Multiple Myeloma (MM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Initially, we searched for such as an association in a large community database and observed a significantly lower MM incidence among SIM users. We proceeded to test the effect of SIM on both murine and human MM cell lines and the tested the effect of long-term SIM treatment on development of MM in an animal model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SIM exposure led to apoptosis in both murine and human MM cell lines. We show that long-term intake of SIM reduced tumor load and positively impacted bone marrow CD8+ T levels as well as cell-mediated anti-myeloma cytotoxicity. SIM treatment also elevated the total IgA and IgG serum concentrations in healthy mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that SIM, which many adults use to control cholesterol levels, may play a dual role in the management of MM, by influencing membrane synthesis in myeloma cells leading to apoptotic cell death and enhancing the T-cell mediated anti-tumor cell response in MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1882291","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:44:40Z","timestamp":1787118280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Simvastatin as an immunomodulator and anti-myeloma agent \u2013 epidemiological, in vitro and murine model studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Aharon","family":"Lion","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Ariel University","place":["Ariel, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arieh Y.","family":"Israel","sequence":"additional","affiliation":[{"name":"Leumit Health Services","place":["Tel Aviv-Yafo, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Merzon","sequence":"additional","affiliation":[{"name":"Leumit Health Services","place":["Tel Aviv-Yafo, Israel"]},{"name":"Department of Hematology, Tel-Aviv Sourasky Medical Center and Tel-Aviv University Medical School","place":["Tel Aviv, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Oster","sequence":"additional","affiliation":[{"name":"Department of Medicine, Tel-Aviv Sourasky Medical Center and Tel-Aviv University Medical School","place":["Tel Aviv, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Weizman","sequence":"additional","affiliation":[{"name":"Research Unit, Geha Mental Health Center, Felsenstein Medical Research Center and Sagol School of Neurosciences, Gray Faculty of Medical and Health Sciences, Tel-Aviv University","place":["Tel-Aviv, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galia","family":"Luboshits","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Ariel University","place":["Ariel, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjarne","family":"Bogen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Mittelman","sequence":"additional","affiliation":[{"name":"Department of 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