CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
β-羟基丁酸增强癌症中 CAR-T 细胞的代谢适应性
英文原题：β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer.
查看英文原题
β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer.
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中文摘要
饮食等生活方式因素对T细胞介导的癌症免疫疗法疗效的影响仍不清楚。在此，我们证明生酮饮食（KD）诱导的酮代谢物β-羟基丁酸（BHB）在多种临床前癌症模型中增强嵌合抗原受体（CAR）T细胞功能。机制上，BHB支持CAR-T 细胞中的三羧酸（TCA）循环，驱动氧化磷酸化和能量生成。这种代谢增强与CAR-T 细胞增殖和细胞因子产生相关，从而导致更优的肿瘤控制。此外，BHB在活化的CAR-T 细胞中诱导全局转录和表观遗传重编程，促进效应和代谢谱的增强。最后，在健康志愿者的前瞻性队列中，给予BHB增强了外周T细胞耗氧量、线粒体膜电位和ATP产生。我们的结果表明，通过BHB补充进行代谢物干预是一种有前景且易于实施的策略，可改善过继T细胞对抗多种癌症的功能。
展开英文摘要原文
The influence of lifestyle factors, such as diet, on the effectiveness of T cell-mediated cancer immunotherapies remains unclear.
Here, we demonstrate that the ketogenic diet (KD)-induced ketone metabolite -hydroxybutyrate (BHB) augments chimeric antigen receptor (CAR) T cell function across multiple preclinical cancer models.
Mechanistically, BHB supports the tricarboxylic acid (TCA) cycle in CAR T cells, driving oxidative phosphorylation and energy generation. This metabolic enhancement is associated with CAR T cell proliferation and cytokine production, thereby leading to superior tumor control.
Furthermore, BHB induces global transcriptional and epigenetic reprogramming in activated CAR T cells, which promotes an enhanced effector and metabolic profile. Lastly, in a prospective cohort of healthy volunteers, administration of BHB enhanced peripheral T cell oxygen consumption, mitochondrial membrane potential, and ATP production.
Our results suggest that metabolite intervention via BHB supplementation is a promising, readily implementable strategy to improve adoptive T cell function against various cancers.
论文信息
- 作者
- Liu S、Guruprasad P、Ramasubramanian R、Madhu B、Paruzzo L、Han K、Kelly A、Shestov A
- 第一作者单位
- Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.United States
- 通讯作者单位
- Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mruella@upenn.edu.United States
- 期刊
- Cell2026 Mar 19
- 原文标识
- PubMed 41794025 · DOI 10.1016/j.cell.2026.02.004