化学辅助衰老T细胞返老还童使老年小鼠对肿瘤免疫治疗敏感

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xue-Feng Bai, Jun-Chi Ma, Cheng Zhang, Zhu Chen, Jinlian He, Si-Xue Cheng, Xian-Zheng Zhang
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引用次数: 0

摘要

大量的资源已经投入到解决肿瘤患者对免疫治疗的次优反应。然而,在这些影响中,一个至关重要但经常被忽视的因素是肿瘤的发生和发展与衰老相关的免疫功能障碍之间的强烈相关性。我们的研究旨在通过靶向递送雷帕霉素(一种能够减轻衰老相关免疫功能下降的大环内酯类药物),使肿瘤引流淋巴结(tdln)内的衰老T细胞恢复活力,从而增强老年小鼠免疫治疗的抗肿瘤功效。靶向递送系统依赖于生物正交反应,利用人工引入tdln上的叠氮化物(N3)基团和附着在皮肤内给药的雷帕霉素胶束上的二苯并环辛(DBCO)基团之间的点击化学作用。实验数据表明,这种方法有效地恢复了老年小鼠受损CD8+ T细胞的功能,从而将免疫检查点阻断(ICB)治疗的抗肿瘤反应提高到与年轻小鼠相当的水平。这项研究提出了一个有希望的策略,以对抗抵抗免疫治疗方法中常见的老年肿瘤患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Click Chemistry-Assisted Rejuvenation of Aging T Cells Sensitizes Aged Mice to Tumor Immunotherapy

Click Chemistry-Assisted Rejuvenation of Aging T Cells Sensitizes Aged Mice to Tumor Immunotherapy
Enormous resources have been devoted to address the suboptimal response of tumor patients to immunotherapy. However, a crucial yet often overlooked factor in these effects is the strong correlation between the occurrence and development of tumors and the immune dysfunction associated with aging. Our study aims to rejuvenate aging T cells within tumor-draining lymph nodes (TdLNs) by using targeted delivery of rapamycin, a macrolide capable of mitigating aging-related decline in immune function, thereby enhancing the antitumor efficacy of immunotherapy in aged mice. The targeted delivery system relies on a bioorthogonal reaction that harnesses the click chemistry between the azide (N3) groups artificially introduced onto TdLNs and the dibenzocyclooctyne (DBCO) groups attached to the rapamycin-loaded micelles administered intradermally. Experimental data demonstrate that this approach has effectively restored the functionality of impaired CD8+ T cells in aged mice, thereby enhancing the antitumor response to immune checkpoint blockade (ICB) therapy to levels comparable to those in young mice. This study presents a promising strategy to combat the resistance to immunotherapeutic approaches commonly encountered among elderly tumor patients.
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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
期刊介绍: The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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