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本能反应:利用微生物代谢为下一代癌症免疫疗法提供动力

Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.

作者信息

Almonte Andrew A, Zitvogel Laurence

机构信息

Clinicobiome, Gustave Roussy Cancer Campus, Villejuif, France.

Equipe Labellisée-Ligue Nationale contre le Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, Villejuif, France.

出版信息

J Immunother Cancer. 2025 Apr 29;13(4):e011540. doi: 10.1136/jitc-2025-011540.


DOI:10.1136/jitc-2025-011540
PMID:40300858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12049984/
Abstract

Immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies, depend heavily on a healthy and diverse gut microbiome for optimal efficacy. Dysbiosis, or an imbalance in gut microbial composition and function, can diminish immunotherapy responses by altering immune cell trafficking and metabolic output. Key microbial metabolites such as short-chain fatty acids and modified bile acids shape host immunity and influence T-cell function, while their disruption can foster an immunosuppressive microenvironment. Emerging strategies to restore a balanced microbiome and boost treatment outcomes include dietary interventions, supplementation with beneficial microbes, and fecal microbiota transplantation. Despite these advances, challenges remain in defining dysbiosis, identifying reliable biomarkers, and tailoring microbiota-centered interventions. Nevertheless, as our understanding evolves, the gut microbiome holds promise as an integral component of personalized cancer immunotherapy.

摘要

免疫疗法,包括免疫检查点抑制剂和嵌合抗原受体T细胞疗法,在很大程度上依赖于健康多样的肠道微生物群来实现最佳疗效。生态失调,即肠道微生物组成和功能的失衡,可通过改变免疫细胞运输和代谢产物来降低免疫疗法的反应。关键的微生物代谢产物,如短链脂肪酸和修饰胆汁酸,塑造宿主免疫力并影响T细胞功能,而它们的破坏会促进免疫抑制微环境。恢复微生物群平衡并提高治疗效果的新兴策略包括饮食干预、补充有益微生物和粪便微生物群移植。尽管取得了这些进展,但在定义生态失调、识别可靠的生物标志物以及定制以微生物群为中心的干预措施方面仍然存在挑战。然而,随着我们认识的不断发展,肠道微生物群有望成为个性化癌症免疫疗法的一个重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c6/12049984/139e0e885c51/jitc-13-4-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c6/12049984/139e0e885c51/jitc-13-4-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c6/12049984/139e0e885c51/jitc-13-4-g001.jpg

相似文献

[1]
Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.

J Immunother Cancer. 2025-4-29

[2]
The role of the gut microbiota in tumor, immunity, and immunotherapy.

Front Immunol. 2024

[3]
Microbiota-centered interventions to boost immune checkpoint blockade therapies.

J Exp Med. 2025-7-7

[4]
From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.

Gut Microbes. 2025-12

[5]
The influence of microbiota on the efficacy and toxicity of immunotherapy in cancer treatment.

Mol Biol Rep. 2024-12-26

[6]
Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes.

Front Immunol. 2024-11-28

[7]
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Arch Toxicol. 2024-8

[8]
Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review.

Front Immunol. 2025-1-7

[9]
Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors.

Cancer Med. 2021-2

[10]
The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer.

IUBMB Life. 2024-12

引用本文的文献

[1]
Effect of Nematodes-Bacteria Complex Metabolites on Cancer and Tumor Progression.

Biomolecules. 2025-8-14

本文引用的文献

[1]
Gut Microbiota-Related Biomarkers in Immuno-Oncology.

Annu Rev Pharmacol Toxicol. 2025-1

[2]
Long-distance microbial mechanisms impacting cancer immunosurveillance.

Immunity. 2024-9-10

[3]
Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy.

NPJ Precis Oncol. 2024-7-16

[4]
Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Nat Med. 2024-9

[5]
Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome.

Cell. 2024-6-20

[6]
Association of Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations.

Cancers (Basel). 2023-12-21

[7]
Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response.

Cell Rep Med. 2023-11-21

[8]
Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.

Nat Med. 2023-8

[9]
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy.

Nat Rev Clin Oncol. 2023-9

[10]
A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.

Science. 2023-6-9

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