基础研究 情报发生 2026-10-31 · 发布于 2026-11-01

清除胞外 DNA 削弱衰老相关抗肿瘤免疫:Dnase1l3 缺失的启示

来源:Front Immunol · PMID 42953061 · DOI 10.3389/fimmu.2026.1965273 · 来源:IMA 知识库《文献层·文献监控卡片》2026-10-31 期 · 全文级(file_id dmlmcfQeUyzO,实际下载核验) · 全文已获取并通过归属校验

时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31

研究问题

While intracellular DNA clearance and sensing mechanisms have been well characterized, extracellular DNA clearance and its associated sensing remain poorly understood.;Hence, we sought to explore how undigested chromatin-bound DNA affects tumor progression in a Dnase1l3-null environment.

方法

Animal experiments were conducted according to guidelines approved by the Institutional Animal Care and Use Committee of Shenzhen Majory Biotechnology Co., Ltd.;Quantification of antibody concentrations was performed using spectrophotometry, and purity was analyzed by gel electrophoresis followed by Coomassie Blue staining.;The sections were fixed and stained with an SA-β-gal (Senescence-associated β-galactosidase) staining Kit (Cell Signaling Technology) according to the instructions ().;Cell counting kit-8 (CCK-8) (#CK04, Dojindo Laboratories) solution was added into the wells, followed by a 2-hour incubation before measurement of the absorbance at 450 nm.

核心结论

However, Dnase1l3 deficiency led to increased serum autoantibodies, including anti-dsDNA and anti-chromatin antibodies, without significantly affecting total serum antibody level ().;In line with the elevated level of serum autoantibodies, Dnase1l3 deficiency also resulted in increased IgG deposition in the tumor tissue ().;Consistently, the serum level of autoantibodies was greatly reduced 2 weeks post αCD20 antibody treatment, while that of total antibody was not significantly affected (, ). ‖ 结论:Notably, although TLR9-mediated senescence is intrinsically an immune defense against genomic insults, our findings suggest that its therapeutic induction—by eliminating both Dnase1l3 and anti-DNA autoantibodies—could offer a cancer immunotherapeutic strategy by driving tumor cells into TLR9-dependent senescence and dormancy.

局限

Therefore, these qPCR data should be interpreted as relative expression trends instead of strict absolute quantitation.;Given that systemic Dnase1l3 inhibition risks autoimmunity and efficacy depends on tumor TLR9 expression, such an approach remains to be validated in future studies.

对本项目的价值

★☆☆☆☆ 相关范围内,作为背景与横向对照收录。

全文来源

PMC JATS 全文(正文 33,960 字符,已过标题/DOI 逐字归属校验)

原文题录

  • 英文标题:Clearance of extracellular DNA prevents senescence-associated antitumor immunity.
  • 期刊与标识:Front Immunol · PMID 42953061 · DOI 10.3389/fimmu.2026.1965273

B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)

本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。

关于本文的文献来源:本站依据 IMA 知识库「五刊监控·深度文献卡片」撰写,依据已获取的期刊全文(方法、样本量与结论已回到原文核对);未能获取全文的同批条目另行标注「摘要级」,全程未做任何数值推算补全。