CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Roles of the gut microbiota in cancer immunotherapy: Mechanistic foundations and therapeutic opportunities.
Roles of the gut microbiota in cancer immunotherapy: Mechanistic foundations and therapeutic opportunities.
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癌症免疫治疗通过免疫检查点阻断、过继细胞治疗、治疗性疫苗和细胞因子疗法等多种方式,彻底改变了肿瘤治疗格局。尽管取得了这些进展,临床反应仍具有异质性,持续获益仅限于少数患者。新出现的证据表明,肠道微生物群是多种治疗平台上免疫治疗疗效的关键系统性调节因子,从机制上将肠道菌群失调与抗肿瘤免疫通过肠道-免疫-肿瘤轴联系起来。特定的共生菌群及其代谢产物,包括短链脂肪酸和色氨酸衍生物,通过增强效应T细胞、激活树突状细胞和抑制调节性T细胞来调控抗肿瘤免疫。本综述系统性地审视了微生物-代谢物-免疫轴,阐明了肠道微生物及代谢物介导免疫治疗反应的机制。
我们全面评估了靶向微生物群的策略,包括饮食干预、益生菌、益生元和粪菌移植,提供了机制见解和转化框架。我们进一步讨论了从关联性微生物组研究向机制性因果关系转变、标准化干预方案以及整合多模态微生态数据方面的当前挑战,并提出了工程化益生菌和精准微生物治疗在现有免疫治疗下优化疗效的未来方向。
Cancer immunotherapy has revolutionized oncological treatment through diverse modalities including immune checkpoint blockade, adoptive cell therapy, therapeutic vaccines, and cytokine-based approaches. Despite these advances, clinical responses remain heterogeneous, with sustained benefit limited to a minority of patients. Emerging evidence now implicates gut microbiota as a critical systemic regulator of immunotherapy efficacy across multiple treatment platforms, mechanistically linking intestinal dysbiosis to antitumor immunity through the gut-immune-tumor axis.
Specific commensal taxa and their metabolites, including short-chain fatty acids and tryptophan derivatives, regulate anti-tumor immunity through effector T cell enhancement, dendritic cell activation, and regulatory T cell suppression. This review systematically examines the microbial-metabolite-immune axis, elucidating mechanisms whereby intestinal microbes and metabolites mediate immunotherapy responses.
We comprehensively evaluate microbiota-targeting strategies including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation, providing mechanistic insights and translational frameworks.
We further discuss current challenges in transitioning from associative microbiome studies to mechanistic causality, standardizing intervention protocols, and integrating multi-modal microecological data, proposing future directions for engineered probiotics and precision microbial therapeutics to optimize outcomes under current immunotherapy.
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