Cited 96 times in
Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model
DC Field | Value | Language |
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dc.contributor.author | 성진실 | - |
dc.date.accessioned | 2018-07-20T07:28:44Z | - |
dc.date.available | 2018-07-20T07:28:44Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/160204 | - |
dc.description.abstract | BACKGROUND & AIMS: Although immunotherapy has emerged as an attractive therapy for refractory cancers, its limited efficacy in hepatocellular carcinoma (HCC) suggests the need for a combination strategy that can either enhance or complement therapeutic effect. We investigated whether combination of immune checkpoint blockade (ICB) and radiation could enhance antitumor effect in a murine HCC model. METHODS: Using murine HCC, HCa-1, the effect of radiation on programmed death-ligand1 (PD-L1) expression was determined by real-time PCR, flow cytometry, and western blotting. Signaling pathways involved in altered PD-L1 expression were examined. Tumor growth and survival rate were evaluated for a combination of anti-PD-L1 and radiation. Immunological parameters in the tumor were assessed using flow cytometry and histological study. RESULTS: Radiation upregulated PD-L1 expression in tumor cells through IFN-γ/STAT3 signaling, which could facilitate therapeutic action of anti-PD-L1. Combination of anti-PD-L1 and radiation significantly suppressed tumor growth compared to treatment with anti-PD-L1 alone or radiation alone group (P<0.01). Survival was significantly improved in the combination group compared to anti-PD-L1 alone or radiation alone group (7-week survival rate; 90% vs. 0% or 30%, respectively, P<0.001). The underlying mechanism involved increasing apoptosis, decreasing tumor cell proliferation, as well as restoration of CD8+ T cell functions. CONCLUSIONS: The combination of anti-PD-L1 and radiation significantly improved the antitumor effect shown in tumor growth delay as well as in survival, supporting a novel combination strategy of immunoradiotherapy in HCC. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Impact Journals | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antibodies, Monoclonal/immunology | - |
dc.subject.MESH | Antibodies, Monoclonal/therapeutic use* | - |
dc.subject.MESH | B7-H1 Antigen/antagonists & inhibitors | - |
dc.subject.MESH | B7-H1 Antigen/immunology | - |
dc.subject.MESH | B7-H1 Antigen/metabolism | - |
dc.subject.MESH | Carcinoma, Hepatocellular/immunology | - |
dc.subject.MESH | Carcinoma, Hepatocellular/metabolism | - |
dc.subject.MESH | Carcinoma, Hepatocellular/therapy* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Combined Modality Therapy | - |
dc.subject.MESH | Hep G2 Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunotherapy/methods | - |
dc.subject.MESH | Liver Neoplasms, Experimental/immunology | - |
dc.subject.MESH | Liver Neoplasms, Experimental/metabolism | - |
dc.subject.MESH | Liver Neoplasms, Experimental/therapy* | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice, Inbred C3H | - |
dc.subject.MESH | Radiotherapy/methods | - |
dc.subject.MESH | STAT3 Transcription Factor/metabolism | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Signal Transduction/radiation effects | - |
dc.subject.MESH | Survival Analysis | - |
dc.subject.MESH | Tumor Burden/drug effects | - |
dc.subject.MESH | Tumor Burden/immunology | - |
dc.subject.MESH | Tumor Burden/radiation effects | - |
dc.title | Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Radiation Oncology | - |
dc.contributor.googleauthor | Kyoung-Jin Kim | - |
dc.contributor.googleauthor | Ji-Hye Kim | - |
dc.contributor.googleauthor | Seo Jin Lee | - |
dc.contributor.googleauthor | Eun-Jung Lee | - |
dc.contributor.googleauthor | Eui-Cheol Shin | - |
dc.contributor.googleauthor | Jinsil Seong | - |
dc.identifier.doi | 10.18632/oncotarget.17168 | - |
dc.contributor.localId | A01956 | - |
dc.relation.journalcode | J02421 | - |
dc.identifier.eissn | 1949-2553 | - |
dc.identifier.pmid | 28465485 | - |
dc.subject.keyword | anti-PD-L1 | - |
dc.subject.keyword | antitumor effect | - |
dc.subject.keyword | combination therapy | - |
dc.subject.keyword | hepatocellular carcinoma | - |
dc.subject.keyword | radiation | - |
dc.contributor.alternativeName | Seong, Jin Sil | - |
dc.contributor.affiliatedAuthor | Seong, Jin Sil | - |
dc.citation.volume | 8 | - |
dc.citation.number | 25 | - |
dc.citation.startPage | 41242 | - |
dc.citation.endPage | 41255 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, Vol.8(25) : 41242-41255, 2017 | - |
dc.identifier.rimsid | 39054 | - |
dc.type.rims | ART | - |
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