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

Analysis of programmed death-ligand 1 expression in primary normal human dermal fibroblasts after DNA damage. Hum Immunol. 2018 May 30;: Authors: Hagiwara Y, Sato H, Permata TBM, Niimi A, Yamauchi M, Oike T, Nakano T, Shibata A 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 upregulati...
Source: Human Immunology - Category: Allergy & Immunology Authors: Tags: Hum Immunol Source Type: research