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亚精胺重塑 TIL(肿瘤浸润淋巴细胞)的线粒体代谢

英文原题:Spermidine Remodels the Mitochondrial Metabolism of Tumor-Infiltrating Lymphocytes.

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Spermidine Remodels the Mitochondrial Metabolism of Tumor-Infiltrating Lymphocytes.

PubMed 2025/10/29(内容时间) J Immunol Res Q3 · IF 3.2(JCR 2025)

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中文摘要

利用TIL(肿瘤浸润淋巴细胞)的过继细胞疗法(ACT)在治疗多种癌症方面具有重要潜力,但TIL容易耗竭和功能障碍,常削弱其疗效。恢复这些关键免疫细胞活力,对于增强抗肿瘤效能至关重要。本研究探讨亚精胺对TIL代谢通路的影响,重点关注其对T细胞活力的关键作用。研究者评估亚精胺对TIL葡萄糖摄取、线粒体功能和能量产生的影响。应用亚精胺后,线粒体功能和能量产生明显改善,表现为线粒体数量增加和三羧酸(TCA)循环活性增强。重要的是,抑制线粒体代谢可消除亚精胺减轻细胞耗竭和增强细胞活性的有益作用,凸显线粒体代谢在亚精胺发挥作用中的必要性。研究提示,利用亚精胺调节代谢,可能增强TIL疗法的抗肿瘤能力,为更好控制实体瘤提供有前景的方法。

展开英文摘要原文

Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has significant potential in treating various cancers; however, its effectiveness is often compromised by the tendency of TILs to become exhausted and dysfunctional. Revitalizing these essential immune cells is crucial for amplifying their antitumor efficacy.

Our study investigates the influence of spermidine on the metabolic pathways of TILs, focusing on its critical contribution to T cell vitality.

We assessed the impact of spermidine on glucose absorption, mitochondrial functionality, and energy production in TILs. The application of spermidine resulted in a pronounced improvement in mitochondrial functionality and energy production, indicated by a surge in mitochondrial numbers and enhanced activity of the tricarboxylic acid (TCA) cycle.

Importantly, the suppression of mitochondrial metabolism negated the beneficial effects of spermidine on mitigating exhaustion and enhancing cellular activity, highlighting the essential role of mitochondrial metabolism in the action of spermidine.

Our research suggests that modulation of metabolism by spermidine could be a potential strategy to strengthen the antitumor capabilities of TIL-based treatments, offering a promising method to better manage solid tumors.

论文信息

作者
Sun Y、Fu H、Li X、Wan M、Xiong H、Zhang C
单位
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China, pku.edu.cn.China
期刊
Journal of immunology research2025
原文标识
PubMed 41179971 · DOI 10.1155/jimr/7550012