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

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

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6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)627-631
Number of pages5
JournalHuman Immunology
Volume79
Issue number8
DOIs
Publication statusPublished - 08-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Hagiwara, Y., Sato, H., Permata, T. B. M., Niimi, A., Yamauchi, M., Oike, T., Nakano, T., & Shibata, A. (2018). Analysis of programmed death-ligand 1 expression in primary normal human dermal fibroblasts after DNA damage. Human Immunology, 79(8), 627-631. https://doi.org/10.1016/j.humimm.2018.05.008