{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:21:08Z","timestamp":1789932068078,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T00:00:00Z","timestamp":1580947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XH-16-110385"],"award-info":[{"award-number":["W81XH-16-110385"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pennies in Action","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Werner and Gertrude Henle Charitable Trust","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>A dendritic cell-based, Type 1 Helper T cell (Th1)-polarizing anti-Human Epidermal Growth Factor Receptor-2 (HER-2) vaccine supplied in the neoadjuvant setting eliminates disease in up to 30% of recipients with HER-2-positive (HER-2pos) ductal carcinoma in situ (DCIS). We hypothesized that drugs with low toxicity profiles that target signaling pathways critical for oncogenesis may work in conjunction with vaccine-induced immune effector mechanisms to improve efficacy while minimizing side effects. In this study, a panel of four phenotypically diverse human breast cancer lines were exposed in vitro to the combination of Th1 cytokines Interferon-gamma (IFN-\u03b3) and Tumor Necrosis Factor-alpha (TNF-\u03b1) and lipophilic statins. This combination was shown to potentiate multiple markers of apoptotic cell death. The combination of statin drugs and Th1 cytokines minimized membrane K-Ras localization while maximizing levels in the cytoplasm, suggesting a possible means by which cytokines and statin drugs might cooperate to maximize cell death. A combined therapy was also tested in vivo through an orthotopic murine model using the neu-transgenic TUBO mammary carcinoma line. We showed that the combination of HER-2 peptide-pulsed dendritic cell (DC)-based immunotherapy and simvastatin, but not single agents, significantly suppressed tumor growth. Consistent with a Th1 cytokine-dependent mechanism, parenterally administered recombinant IFN-\u03b3 could substitute for DC-based immunotherapy, likewise inhibiting tumor growth when combined with simvastatin. These studies show that statin drugs can amplify a DC-induced effector mechanism to improve anti-tumor activity.<\/jats:p>","DOI":"10.3390\/vaccines8010072","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T03:13:27Z","timestamp":1581045207000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Statin Drugs Plus Th1 Cytokines Potentiate Apoptosis and Ras Delocalization in Human Breast Cancer Lines and Combine with Dendritic Cell-Based Immunotherapy to Suppress Tumor Growth in a Mouse Model of HER-2pos Disease"],"prefix":"10.3390","volume":"8","author":[{"given":"Crystal M.","family":"Oechsle","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA"},{"name":"Ohio Attorney General\u2019s Center for the Future of Forensic Science, Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loral E.","family":"Showalter","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Kent State University, Kent, OH 44242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brain J.","family":"Czerniecki","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-7767","authenticated-orcid":false,"given":"Gary K.","family":"Koski","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1200\/JCO.1993.11.10.1936","article-title":"Clinical significance of HER-2\/neu oncogene amplification in primary breast cancer. 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