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微生物群衍生代谢物:癌症免疫疗法的关键调节因子

英文原题:Microbiota-derived metabolites: Key modulators of cancer immunotherapies.

查看英文原题

Microbiota-derived metabolites: Key modulators of cancer immunotherapies.

PubMed 2025/07/21(内容时间) Med Q1 · IF 13.3(JCR 2025)

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中文摘要

人体肠道微生物组塑造局部和全身免疫反应,并影响癌症免疫治疗结局。微生物代谢物,包括短链和支链脂肪酸、胆汁酸、色氨酸衍生物等,通过调节免疫细胞、肿瘤生长和肿瘤微环境来影响抗肿瘤免疫。这些代谢物影响免疫检查点抑制剂、异基因干细胞移植、CAR-T 细胞疗法的疗效以及免疫相关不良事件。然而,个体间微生物组变异性、抗生素暴露以及代谢物依赖背景的促炎和抗炎效应,为临床转化带来了重大挑战。基于微生物组的疗法,包括活体生物治疗产品、饮食调整(如益生元)和合成代谢物化合物(后生元),正在被开发用于与免疫治疗联合使用。本综述概述了代谢物如何影响免疫治疗结局,并讨论了将其用于临床实践的转化方法。未来研究应侧重于验证基于代谢物的生物标志物,并定制基于代谢物的干预措施,以提高不同免疫治疗的疗效并降低毒性。

展开英文摘要原文

The human gut microbiome shapes local and systemic immune responses and influences cancer immunotherapy outcomes. Microbial metabolites, including short-chain and branched-chain fatty acids, bile acids, tryptophan derivatives, and others, influence anti-tumor immunity by modulating immune cells, tumor growth, and the tumor microenvironment. These metabolites impact the efficacy of immune checkpoint inhibitors, allogeneic stem cell transplantation, chimeric antigen receptor T cell therapies, and immune-related adverse events.

However, interindividual microbiome variability, antibiotic exposure, and the context-dependent pro- and anti-inflammatory effects of metabolites present significant challenges for clinical translation. Microbiome-based therapies, including live biotherapeutic products, dietary modifications (such as prebiotics), and synthetic metabolite compounds (postbiotics), are being developed for use in combination with immunotherapy.

This review outlines how metabolites influence immunotherapy outcomes and discusses translational approaches to harness them for clinical practice. Future research should focus on validating metabolite-based biomarkers and tailoring metabolite-based interventions to enhance efficacy and reduce toxicity across different immunotherapies.

论文信息

作者
Perl M、Fante MA、Herfeld K、Scherer JN、Poeck H、Thiele Orberg E
第一作者单位
Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany.Germany
通讯作者单位
Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany. Electronic address: erik.orberg@ukr.de.Germany
文献类型
综述 · 非美国政府资助研究
期刊
Med (New York, N.Y.)2025 Aug 8
原文标识
PubMed 40695291 · DOI 10.1016/j.medj.2025.100773