基础研究

靶向线粒体代谢重编程的放疗增敏偶联物诱发焦亡并激活抗肿瘤免疫

来源:Science advances · PMID 42962039 · DOI 10.1126/sciadv.aeh5903 · 来源:IMA 知识库《文献层·文献监控卡片》2026-11-01 期 · 全文级(file_id dlMXdlgtPZzo,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 2026-11-01 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/31–2026/11/01 | 情报发生日期 2026-11-01

研究问题

Furthermore, integration with anti–PD-L1 (αPD-L1) immune checkpoint blockade (ICB) markedly suppressed both primary and distant tumor growth in a bilateral triple-negative breast cancer model and nearly eliminated pulmonary metastasis.;Together, these findings establish a MOF-based radiometabolic strategy that enhances RT efficacy while promoting durable systemic antitumor immunity.

方法

Statistical analysis Statistical analysis was performed using GraphPad Prism (10.0).;CT26 and 4T1 cells were maintained in Dulbecco’s modified Eagle’s medium or RPMI 1640, respectively, supplemented with 10% fetal bovine serum (FBS), penicillin (100 U/ml), and streptomycin (100 μg/ml).;All animal experiments were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Chicago [PHS Assurance #D16-00322 (A3523-01)].

核心结论

We found that Hf-Ir/DON(+) markedly reduced activation-induced CD8 + T cell death and promoted a shift toward a memory-associated phenotype, characterized by increased T cm cells and reduced exhaustion signatures.;Compared with PBS(+) and Hf-Ir(+) groups, Hf-Ir/DON(+) treatment significantly reduced the proportion of viable cells while markedly increasing the proportion of PI-positive necrotic/pyroptotic cells.;Both Hf-Ir/DON(+) treatment and combination treatment preserved splenic germinal center architecture, reduced spleen weight, and markedly decreased the number of pulmonary metastatic nodules ( and fig.;Concurrently, Hf-Ir/DON(+) significantly improved CD8 + T cell survival ( ), reducing the fraction of dead CD8 + T cells to 24.4 ± 2.1% compared with 55.5 ± 2.8% for PBS(+) and 52.2 ± 2.7% for Hf-Ir(+).

局限

Briefly, bone marrow cells were flushed from femurs and tibias, passed through a 70-μm cell strainer, and subjected to red blood cell lysis.;In this study, we uncover an integrated radiometabolic nanoradioimmunotherapy strategy that addresses these limitations.

对本项目的价值

中等价值:线粒体代谢重编程驱动焦亡以增强放疗抗肿瘤免疫 —— 与衰老弱相关,主要作为线粒体—免疫交叉机制参考。 | 价值分 3.7/5(★★★★☆)

全文来源

PubMed PMC JATS 全文(正文 72,434 字符,已过 DOI 逐字 + 题名指纹双重归属校验)

原文题录

  • 英文标题:Mitochondrial metabolic reprogramming by a glutamine antagonist radioenhancer conjugate drives pyroptosis and antitumor immunity.
  • 期刊与标识:Science advances · PMID 42962039 · DOI 10.1126/sciadv.aeh5903

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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