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代谢对话:肿瘤微环境中 CAR-T 细胞功能的调控因子

英文原题:Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment.

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Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment.

PubMed 2024/06/22(内容时间) Mol Oncol Q2 · IF 4.5(JCR 2025)

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中文摘要

TIL(肿瘤浸润淋巴细胞)已用于复发/难治性黑色素瘤治疗,CAR-T 则在血液系统恶性肿瘤中取得显著成功,推动了癌症治疗模式转变。这些“活药物”的效果取决于其在患者体内增殖和持续存在的能力。研究显示,调节这些功能及T细胞分化状态的机制受代谢变化和代谢通路利用影响。营养供给以及细胞表面代谢物转运蛋白表达会影响这些变化,并与信号通路和表观遗传状态相互作用,进而改变基因表达及蛋白调控。本文综述活化T细胞代谢重塑、肿瘤代谢环境对T细胞功能的影响,以及增强T细胞免疫疗法的潜在代谢干预策略。

展开英文摘要原文

Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in the treatment of relapsed/refractory melanoma and hematological malignancies, respectively. These treatments have marked a pivotal shift in cancer management.

However, as "living drugs," their effectiveness is dependent on their ability to proliferate and persist in patients. Recent studies indicate that the mechanisms regulating these crucial functions, as well as the T cell's differentiation state, are conditioned by metabolic shifts and the distinct utilization of metabolic pathways.

These metabolic shifts, conditioned by nutrient availability as well as cell surface expression of metabolite transporters, are coupled to signaling pathways and the epigenetic landscape of the cell, modulating transcriptional, translational, and post-translational profiles. In this review, we discuss the processes underlying the metabolic remodeling of activated T cells, the impact of a tumor metabolic environment on T cell function, and potential metabolic-based strategies to enhance T cell immunotherapy.

论文信息

作者
Moraly J、Kondo T、Benzaoui M、DuSold J、Talluri S、Pouzolles MC、Chien C、Dardalhon V
单位
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.United States
文献类型
综述 · 美国 NIH 资助研究 · 非美国政府资助研究
期刊
Molecular oncology2024 Jul
原文标识
PubMed 38922759 · DOI 10.1002/1878-0261.13691