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代谢物作为肿瘤免疫治疗的药物与靶点

英文原题:Metabolites as agents and targets for cancer immunotherapy.

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Metabolites as agents and targets for cancer immunotherapy.

PubMed 2025/06/26(内容时间) Nat Rev Drug Discov Q1 · IF 91.2(JCR 2025)

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中文摘要

肿瘤微环境中代谢物的耗竭或积累是癌症的标志之一,但针对癌细胞代谢的治疗也必须考虑对免疫细胞代谢途径的影响。随着我们对免疫代谢的理解不断深入,调节代谢的药物与免疫治疗之间出现了协同作用的机会。在这篇综述中,我们讨论了代谢途径在癌细胞和免疫细胞中塑造肿瘤微环境的关键作用。我们概述了主要的合成代谢和分解代谢途径,并讨论了代谢调节剂和膳食营养素如何改善抗癌免疫反应并克服耐药机制。临床上的药物包括腺苷和色氨酸途径的抑制剂,我们讨论了在免疫检查点阻断和嵌合抗原受体(CAR)-T细胞治疗背景下成功开发药物的机遇和挑战。

展开英文摘要原文

The depletion or accumulation of metabolites in the tumour microenvironment is one of the hallmarks of cancer, but targeting cancer cell metabolism therapeutically must also take into account the impact on metabolic pathways in immune cells. As we understand more about immunometabolism, opportunities arise for synergies between agents that modulate metabolism and immunotherapy. In this Review, we discuss the pivotal role of metabolic pathways in both cancer and immune cells in shaping the tumour microenvironment.

We survey major anabolic and catabolic pathways and discuss how metabolic modulators and dietary nutrients can improve the anticancer immune response and overcome drug resistance mechanisms. Agents in the clinic include inhibitors of the adenosine and tryptophan pathways, and we discuss opportunities and challenges for successful drug development in the context of immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapies.

论文信息

作者
Trefny MP、Kroemer G、Zitvogel L、Kobold S
第一作者单位
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.Germany
通讯作者单位
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany. sebastian.kobold@med.uni-muenchen.de.Germany
文献类型
综述
期刊
Nature reviews. Drug discovery2025 Oct
原文标识
PubMed 40571788 · DOI 10.1038/s41573-025-01227-z