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了解肠道微生物群在实体瘤对免疫检查点抑制剂反应中的作用以制定个性化治疗策略:综述

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

作者信息

Lim Mi Young, Hong Seungpyo, Nam Young-Do

机构信息

Personalized Diet Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea.

Department of Molecular Biology, Jeonbuk National University, Jeonju-si, Jeollabuk-do, Republic of Korea.

出版信息

Front Immunol. 2025 Jan 7;15:1512683. doi: 10.3389/fimmu.2024.1512683. eCollection 2024.

Abstract

Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.

摘要

免疫疗法,尤其是免疫检查点抑制剂(ICI)疗法,已使一些实体癌患者取得了显著疗效,但其他患者对这些治疗并无反应。最近的研究已确定肠道微生物群是免疫反应的关键调节因子,这表明其组成与癌症治疗中对ICI疗法的反应密切相关。因此,肠道微生物群作为预测个体对ICI疗法反应的潜在生物标志物以及增强治疗效果的靶点正受到关注。在本综述中,我们讨论了来自人类观察性研究的关键发现,这些研究评估了ICI治疗前使用抗生素对治疗结果的影响,并确定了与有利和不利反应相关的特定肠道细菌。此外,我们回顾了在开始ICI治疗前使用基于肠道微生物群数据的机器学习模型预测患者预后可能性的研究,以及探索肠道微生物群调节(例如通过粪便微生物群移植或活生物治疗产品)是否能改善癌症患者ICI治疗效果的临床试验。我们还简要讨论了肠道微生物衍生产物影响免疫治疗效果的机制。有必要进行进一步研究,以充分了解宿主、肠道微生物群和免疫治疗之间的复杂相互作用,并制定优化对ICI疗法反应的个性化策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6c/11747443/37473a97ff82/fimmu-15-1512683-g001.jpg

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