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。
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