論文

査読有り 国際誌
2018年8月

Analysis of programmed death-ligand 1 expression in primary normal human dermal fibroblasts after DNA damage.

Human immunology
  • Yoshihiko Hagiwara
  • ,
  • Hiro Sato
  • ,
  • Tiara Bunga Mayang Permata
  • ,
  • Atsuko Niimi
  • ,
  • Motohiro Yamauchi
  • ,
  • Takahiro Oike
  • ,
  • Takashi Nakano
  • ,
  • Atsushi Shibata

79
8
開始ページ
627
終了ページ
631
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.humimm.2018.05.008

Programmed cell death-1 (PD-1) and its ligand (programmed death-ligand 1, PD-L1) are key factors that regulate a cytotoxic immune reaction. Anti-PD-1 therapy provides significant clinical benefits for patients with cancer, even those with advanced-stage cancer. We have recently demonstrated that DNA damage signaling from DNA double-strand breaks (DSBs) promotes PD-L1 upregulation in cancer cells. In the present study, we aimed to investigate PD-L1 expression in primary normal human dermal fibroblasts (NHDFs) in response to DSBs. We demonstrated that PD-L1 expression in NHDFs is not upregulated after ionizing radiation (IR). In addition, interferon (IFN) regulatory factor 1 (IRF1) and signal transducer and activator of transcription 1 (STAT1) phosphorylation do not respond in NHDFs after IR. In contrast, IFNγ treatment upregulates PD-L1 and IRF1 expressions and STAT1 phosphorylation. The nonresponsiveness was also observed after treatment with other DNA-damaging agents, such as camptothecin and etoposide. Treatment with a histone deacetylase inhibitor (HDACi), which causes chromatin relaxation and restores gene silencing, upregulates PD-L1 without exogenous DNA damage; however, IR-dependent upregulation is not observed in NHDFs treated with HDACi. Taken together, our data suggest that DNA-damage signaling is insufficient for upregulating PD-L1 in NHDFs.

リンク情報
DOI
https://doi.org/10.1016/j.humimm.2018.05.008
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29859207
ID情報
  • DOI : 10.1016/j.humimm.2018.05.008
  • PubMed ID : 29859207

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