{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:48:57Z","timestamp":1785174537120,"version":"3.55.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020MH330"],"award-info":[{"award-number":["ZR2020MH330"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012905","name":"Department of Science and Technology of Shandong Province","doi-asserted-by":"publisher","award":["2019GSF108083"],"award-info":[{"award-number":["2019GSF108083"]}],"id":[{"id":"10.13039\/100012905","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472800"],"award-info":[{"award-number":["81472800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>An abscopal effect occurs when localized radiotherapy causes the regression of tumors distant from the irradiated site. However, such a clinically detectable abscopal effect from radiotherapy alone is rare. This study investigated whether valproic acid ([VPA], a histone deacetylase inhibitor [HDACi]) treatment can stimulate radiation-induced abscopal effect. We used 7,12-dimethylbenz[a]anthracene, a typical environmental carcinogen, to establish a rat model with multiple breast tumors. Only one tumor received 8 Gy fractionated doses of X-rays (2 Gy daily fractions over four days) and 200\u00a0mg\/kg VPA was administered intraperitoneally. We monitored the growth of both irradiated and unirradiated tumors after treatments. The unirradiated tumor was collected for hematoxylin and eosin (HE) staining, immunohistochemistry (IHC) (CD8, Granzyme B, Cleaved Caspase-3, BrdU, Ki67, F4\/80 and CD68), double immunofluorescence (F4\/80 and CD86), Western blot (Cleaved Caspase-3) and qRT-PCR (CD86, CD163, IL-1\u03b2, IL-6, IL-12, IL-23, IL-10, TGF-\u03b2) analysis. We found ionizing radiation (IR)\u2009+\u2009VPA treatment inhibited both irradiated and unirradiated tumor growth as compared to IR alone. Such observe abscopal effect was mediated by the recruitment of activated CD8+ T cells into the unirradiated tumor sites, which released Granzyme B to cause tumor cell apoptosis. Furthermore, IR\u2009+\u2009VPA treatment led to macrophages infiltration into the unirradiated tumor sites and polarization to M1 phenotype, resulted in increased levels of pro-inflammatory cytokines such as IL-1\u03b2 and IL-12, and decreased levels of anti-inflammatory cytokines such as IL-10 and TGF-\u03b2. Our data supports the proposition that VPA may be a potential therapeutic candidate to trigger radiation-induced abscopal effect by modulating the unirradiated tumor immune microenvironment.<\/jats:p>","DOI":"10.1093\/jrr\/rrab037","type":"journal-article","created":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T05:41:41Z","timestamp":1622266901000},"source":"Crossref","is-referenced-by-count":8,"title":["Valproic acid triggers radiation-induced abscopal effect by modulating the unirradiated tumor immune microenvironment in a rat model of breast cancer"],"prefix":"10.1093","author":[{"given":"Liya","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuchao","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Western Sydney University, Campbelltown 2560, Australia"},{"name":"College of Medicine and Public Health, Flinders University, Bedford Place 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"2021070802552349400_ref1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/bjc.2011.240","article-title":"Guidelines for preclinical and early phase clinical assessment of novel radiosensitisers","volume":"105","author":"Harrington","year":"2011","journal-title":"Br J Cancer"},{"key":"2021070802552349400_ref2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nrclinonc.2015.120","article-title":"Opportunities and challenges of radiotherapy for treating cancer","volume":"12","author":"Schaue","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"key":"2021070802552349400_ref3","doi-asserted-by":"crossref","first-page":"927","DOI":"10.3390\/ijms15010927","article-title":"The effect of radiation on the immune response to 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