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Title: Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy
Authors: Hatae, Ryusuke
Chamoto, Kenji
Kim, Young Hak
Sonomura, Kazuhiro
Taneishi, Kei
Kawaguchi, Shuji
Yoshida, Hironori
Ozasa, Hiroaki
Sakamori, Yuichi
Akrami, Maryam
Fagarasan, Sidonia
Masuda, Izuru
Okuno, Yasushi
Matsuda, Fumihiko
Hirai, Toyohiro
Honjo, Tasuku
Author's alias: 波多江, 龍亮
茶本, 健司
金, 永学
園村, 和弘
種石, 慶
川口, 修治
吉田, 博徳
小笹, 裕晃
阪森, 優一
枡田, 出
奥野, 恭史
松田, 文彦
平井, 豊博
本庶, 佑
Issue Date: 30-Jan-2020
Publisher: American Society for Clinical Investigation
Journal title: JCI Insight
Volume: 5
Issue: 2
Thesis number: e133501
Abstract: BACKGROUND. 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.
Description: PD-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.
Rights: © 2020, American Society for Clinical Investigation
Publisher permitted to deposit this paper on this repository.
DOI(Published Version): 10.1172/jci.insight.133501
PubMed ID: 31855576
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