DNA损伤
癌症研究
生物
三阴性乳腺癌
干扰素基因刺激剂
DNA修复
干扰素
组蛋白
阿霉素
免疫系统
DNA
免疫学
癌症
乳腺癌
化疗
先天免疫系统
遗传学
作者
Na-Lee Ka,Ga Young Lim,Sung Ho Hwang,Seung-Su Kim,Mi‐Ock Lee
出处
期刊:Cell Reports
[Elsevier]
日期:2021-12-01
卷期号:37 (12): 110138-110138
被引量:25
标识
DOI:10.1016/j.celrep.2021.110138
摘要
Tumor DNA-damage response (DDR) has an important role in driving type-I interferon (IFN)-mediated host antitumor immunity, but it is not clear how tumor DNA damage is interconnected with the immune response. Here, we report the role of IFN-γ-inducible protein 16 (IFI16) in DNA repair, which amplifies the stimulator of IFN genes (STING)-type-I IFN signaling, particularly in triple-negative breast cancer (TNBC). IFI16 is rapidly induced and accumulated to the histone-evicted DNA at double-stranded breakage (DSB) sites, where it inhibits recruitment of DDR factors. Subsequently, IFI16 increases the release of DNA fragments to the cytoplasm and induces STING-mediated type-I IFN production. Synergistic cytotoxic and immunomodulatory effects of doxorubicin and type-I IFNs are decreased upon IFI16 depletion in vivo. Furthermore, IFI16 expression correlates with improved clinical outcome in patients with TNBC treated with chemotherapy. Together, our findings suggest that type-I IFNs and IFI16 could offer potential therapeutic strategies for TNBC.
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