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肠道微生物群的多样性和组成在预测黑色素瘤患者免疫治疗反应及免疫治疗相关结肠炎中的作用:一项系统评价

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review.

作者信息

Oey Oliver, Liu Yu-Yang, Sunjaya Angela Felicia, Simadibrata Daniel Martin, Khattak Muhammad Adnan, Gray Elin

机构信息

Department of Medical Oncology, St John of God Midland Public and Private Hospital, Midland, Perth 6004, WA, Australia.

School of Medicine, University of Western Australia, Perth 6009, WA, Australia.

出版信息

World J Clin Oncol. 2022 Nov 24;13(11):929-942. doi: 10.5306/wjco.v13.i11.929.

Abstract

BACKGROUND

Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis.

AIM

To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.

METHODS

The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis () (https://www.referencecitationanalysis.com).

RESULTS

Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis ( 0.01) whereas samples enriched in were more resistant to ICB-related colitis ( 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results.

CONCLUSION

This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

摘要

背景

肠道微生物群(GM)的组成和多样性最近被作为免疫检查点阻断疗法(ICB)反应及ICB相关结肠炎的生物标志物进行研究。

目的

对GM组成和多样性在预测接受ICB治疗的黑色素瘤患者的反应及结肠炎方面的作用进行系统评价。

方法

该评价方案已在国际前瞻性系统评价注册库(PROSPERO)登记:CRD42021228018。在总共300项研究中,9项研究符合纳入标准。2项研究为I期临床试验,其余为前瞻性观察性研究。除1项研究外,所有研究均有中度偏倚风险。此外,我们通过参考文献引用分析(https://www.referencecitationanalysis.com)进行了相关检索。

结果

富含厚壁菌门的粪便样本与对ICB的良好反应相关,而拟杆菌目家族与对ICB的不良反应相关。GM多样性更高的样本与对ICB更有利的反应相关[风险比(HR)=3.57,95%置信区间=1.02 - 12.52,P<0.05]。厚壁菌门丰度较高的粪便样本更容易发生ICB相关结肠炎(P<0.01),而富含[此处原文缺失相关菌群名称]的样本对ICB相关结肠炎更具抵抗力(P<0.05)。总体而言,在已确定与ICB反应相关的GM中的微生物方面,一致性有限,且评估GM多样性的研究结果相互矛盾。

结论

这突出表明需要进一步的前瞻性研究,以确认GM是否可作为生物标志物以及调节黑色素瘤患者ICB反应的潜在干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/9724183/b94e355e2ce0/WJCO-13-929-g001.jpg

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