論文

査読有り 国際誌
2022年12月14日

Combination bezafibrate and nivolumab treatment of patients with advanced non-small cell lung cancer.

Science translational medicine
  • Kentaro Tanaka
  • Kenji Chamoto
  • Sho Saeki
  • Ryusuke Hatae
  • Yuki Ikematsu
  • Kazuko Sakai
  • Nobuhisa Ando
  • Kazuhiro Sonomura
  • Shinsuke Kojima
  • Masanori Taketsuna
  • Young Hak Kim
  • Hironori Yoshida
  • Hiroaki Ozasa
  • Yuichi Sakamori
  • Tomoko Hirano
  • Fumihiko Matsuda
  • Toyohiro Hirai
  • Kazuto Nishio
  • Takuro Sakagami
  • Masanori Fukushima
  • Yoichi Nakanishi
  • Tasuku Honjo
  • Isamu Okamoto
  • 全て表示

14
675
開始ページ
eabq0021
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/scitranslmed.abq0021
出版者・発行元
American Association for the Advancement of Science (AAAS)

Despite the success of cancer immunotherapies such as programmed cell death–1 (PD-1) and PD-1 ligand 1 (PD-L1) inhibitors, patients often develop resistance. New combination therapies with PD-1/PD-L1 inhibitors are needed to overcome this issue. Bezafibrate, a ligand of peroxisome proliferator–activated receptor–γ coactivator 1α/peroxisome proliferator–activated receptor complexes, has shown a synergistic antitumor effect with PD-1 blockade in mice that is mediated by activation of mitochondria in T cells. We have therefore now performed a phase 1 trial (UMIN000017854) of bezafibrate with nivolumab in previously treated patients with advanced non–small cell lung cancer. The primary end point was the percentage of patients who experience dose-limiting toxicity, and this combination regimen was found to be well tolerated. Preplanned comprehensive analysis of plasma metabolites and gene expression in peripheral cytotoxic T cells indicated that bezafibrate promoted T cell function through up-regulation of mitochondrial metabolism including fatty acid oxidation and may thereby have prolonged the duration of response. This combination strategy targeting T cell metabolism thus has the potential to maintain antitumor activity of immune checkpoint inhibitors and warrants further validation.

リンク情報
DOI
https://doi.org/10.1126/scitranslmed.abq0021
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/36516270
ID情報
  • DOI : 10.1126/scitranslmed.abq0021
  • ISSN : 1946-6234
  • eISSN : 1946-6242
  • PubMed ID : 36516270

エクスポート
BibTeX RIS