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dc.contributor.authorHatae, Ryusukeen
dc.contributor.authorChamoto, Kenjien
dc.contributor.authorKim, Young Haken
dc.contributor.authorSonomura, Kazuhiroen
dc.contributor.authorTaneishi, Keien
dc.contributor.authorKawaguchi, Shujien
dc.contributor.authorYoshida, Hironorien
dc.contributor.authorOzasa, Hiroakien
dc.contributor.authorSakamori, Yuichien
dc.contributor.authorAkrami, Maryamen
dc.contributor.authorFagarasan, Sidoniaen
dc.contributor.authorMasuda, Izuruen
dc.contributor.authorOkuno, Yasushien
dc.contributor.authorMatsuda, Fumihikoen
dc.contributor.authorHirai, Toyohiroen
dc.contributor.authorHonjo, Tasukuen
dc.contributor.alternative波多江, 龍亮ja
dc.contributor.alternative茶本, 健司ja
dc.contributor.alternative金, 永学ja
dc.contributor.alternative園村, 和弘ja
dc.contributor.alternative種石, 慶ja
dc.contributor.alternative川口, 修治ja
dc.contributor.alternative吉田, 博徳ja
dc.contributor.alternative小笹, 裕晃ja
dc.contributor.alternative阪森, 優一ja
dc.contributor.alternative枡田, 出ja
dc.contributor.alternative奥野, 恭史ja
dc.contributor.alternative松田, 文彦ja
dc.contributor.alternative平井, 豊博ja
dc.contributor.alternative本庶, 佑ja
dc.date.accessioned2020-02-05T06:49:53Z-
dc.date.available2020-02-05T06:49:53Z-
dc.date.issued2020-01-30-
dc.identifier.issn2379-3708-
dc.identifier.urihttp://hdl.handle.net/2433/245622-
dc.descriptionPD-1抗体がん免疫治療の有効性を判別するバイオマーカーを同定 --血液検査のみで有効性の診断が可能に--. 京都大学プレスリリース. 2020-01-31.ja
dc.description.abstractBACKGROUND. Current clinical biomarkers for the programmed cell death 1 (PD-1) blockade therapy are insufficient because they rely only on the tumor properties, such as programmed cell death ligand 1 expression frequency and tumor mutation burden. Identifying reliable, responsive biomarkers based on the host immunity is necessary to improve the predictive values. METHODS. We investigated levels of plasma metabolites and T cell properties, including energy metabolism markers, in the blood of patients with non-small cell lung cancer before and after treatment with nivolumab (n = 55). Predictive values of combination markers statistically selected were evaluated by cross-validation and linear discriminant analysis on discovery and validation cohorts, respectively. Correlation between plasma metabolites and T cell markers was investigated. RESULTS. The 4 metabolites derived from the microbiome (hippuric acid), fatty acid oxidation (butyrylcarnitine), and redox (cystine and glutathione disulfide) provided high response probability (AUC = 0.91). Similarly, a combination of 4 T cell markers, those related to mitochondrial activation (PPARγ coactivator 1 expression and ROS), and the frequencies of CD8+PD-1hi and CD4+ T cells demonstrated even higher prediction value (AUC = 0.96). Among the pool of selected markers, the 4 T cell markers were exclusively selected as the highest predictive combination, probably because of their linkage to the abovementioned metabolite markers. In a prospective validation set (n = 24), these 4 cellular markers showed a high accuracy rate for clinical responses of patients (AUC = 0.92). CONCLUSION. Combination of biomarkers reflecting host immune activity is quite valuable for responder prediction.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherAmerican Society for Clinical Investigationen
dc.rights© 2020, American Society for Clinical Investigationen
dc.rightsPublisher permitted to deposit this paper on this repository.en
dc.titleCombination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapyen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleJCI Insighten
dc.identifier.volume5-
dc.identifier.issue2-
dc.relation.doi10.1172/jci.insight.133501-
dc.textversionpublisher-
dc.identifier.artnume133501-
dc.identifier.pmid31855576-
dc.relation.urlhttps://www.kyoto-u.ac.jp/ja/research-news/2020-01-31-
dcterms.accessRightsopen access-
datacite.awardNumber16H06149-
datacite.awardNumber17K19593-
datacite.awardNumber19K17673-
jpcoar.funderName日本学術振興会ja
jpcoar.funderName日本学術振興会ja
jpcoar.funderName日本学術振興会ja
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
出現コレクション:学術雑誌掲載論文等

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