Microsatellite Instability in the Tumor Microenvironment: The Role of Inflammation and the Microbiome

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-04-15 DOI:10.1002/cam4.70603

Elizabeth Vargas-Castellanos, Andrés Rincón-Riveros

{"title":"Microsatellite Instability in the Tumor Microenvironment: The Role of Inflammation and the Microbiome","authors":"Elizabeth Vargas-Castellanos, Andrés Rincón-Riveros","doi":"10.1002/cam4.70603","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Microsatellite instability (MSI) is a hallmark of DNA mismatch repair (MMR) deficiency that leads to genomic instability and increased cancer risk. The tumor microenvironment (TME) significantly influences MSI-driven tumorigenesis, and emerging evidence points to a critical role of the microbiome in shaping this complex interplay.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This review comprehensively examines the existing literature on the intricate relationship between MSI, microbiome, and cancer development, with a particular focus on the impact of microbial dysbiosis on the TME.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>MSI-high tumors exhibited increased immune cell infiltration owing to the generation of neoantigens. However, immune evasion mechanisms such as PD-1/CTLA-4 upregulation limit the efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients. Pathobionts, such as Fusobacterium nucleatum and Bacteroides fragilis, contribute to MSI through the production of genotoxins, further promoting inflammation and oxidative stress within the TME.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 8","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70603","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70603","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Microsatellite instability (MSI) is a hallmark of DNA mismatch repair (MMR) deficiency that leads to genomic instability and increased cancer risk. The tumor microenvironment (TME) significantly influences MSI-driven tumorigenesis, and emerging evidence points to a critical role of the microbiome in shaping this complex interplay.

Methods

This review comprehensively examines the existing literature on the intricate relationship between MSI, microbiome, and cancer development, with a particular focus on the impact of microbial dysbiosis on the TME.

Results

MSI-high tumors exhibited increased immune cell infiltration owing to the generation of neoantigens. However, immune evasion mechanisms such as PD-1/CTLA-4 upregulation limit the efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients. Pathobionts, such as Fusobacterium nucleatum and Bacteroides fragilis, contribute to MSI through the production of genotoxins, further promoting inflammation and oxidative stress within the TME.

Conclusions

The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.

Abstract Image

查看原文本刊更多论文

肿瘤微环境中的微卫星不稳定性：炎症和微生物组的作用

背景微卫星不稳定性（MSI）是 DNA 错配修复（MMR）缺陷的标志，会导致基因组不稳定和癌症风险增加。肿瘤微环境（TME）对 MSI 驱动的肿瘤发生有重大影响，而新出现的证据表明微生物组在形成这种复杂的相互作用方面起着关键作用。方法本综述全面研究了有关 MSI、微生物组和癌症发展之间错综复杂关系的现有文献，尤其关注微生物菌群失调对肿瘤微环境的影响。结果 MSI高的肿瘤由于产生新抗原而表现出免疫细胞浸润增加。然而，PD-1/CTLA-4 上调等免疫逃避机制限制了免疫检查点抑制剂（ICIs）在部分患者中的疗效。病原菌（如核酸镰刀菌和脆弱拟杆菌）通过产生基因毒素导致 MSI，并进一步促进 TME 内的炎症和氧化应激。结论微生物群对 MSI 驱动的肿瘤发生有深远影响。通过粪便微生物群移植、益生菌和饮食改变等干预措施来调节肠道微生物群，有望提高 ICI 反应率。进一步研究癌症药物微生物组学，调查微生物代谢物与抗癌疗法之间的相互作用，对于制定个性化治疗策略至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.