{"title":"The immune microenvironment of colorectal cancer.","authors":"Kilian B Kennel,Florian R Greten","doi":"10.1038/s41568-025-00872-1","DOIUrl":null,"url":null,"abstract":"Colorectal cancer (CRC) progression depends on the close interaction of tumour cells and the tumour microenvironment (TME). Although the TME contributes to poor therapy responses and immune evasion, immune cells within the TME can be therapeutically leveraged, as exemplified by immune checkpoint blockade (ICB). Unfortunately, only a small subset of patients with CRC benefit from ICB therapy; those with immune-activated, microsatellite unstable CRC respond, whereas the predominant group of patients with CRC, those with microsatellite-stable tumours, do not. Although challenging, modulating the TME of CRC to convert these lowly immunogenic and immunosuppressed tumours into immune-activated tumours holds tremendous therapeutic potential. In this Review we provide an overview of the cellular and molecular components of immunity in the TME of CRCs at various stages of disease as well as the mechanisms of immunosuppression and immune evasion. We further describe how systemic and local therapies for CRC impact the tumour and systemic immune microenvironments, and how immunity could serve as a therapeutic and prognostic biomarker. Lastly, we highlight novel immunotherapeutic strategies and approaches that modulate the TME of CRCs to make them amenable to immunotherapy.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"40 1","pages":""},"PeriodicalIF":66.8000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41568-025-00872-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Colorectal cancer (CRC) progression depends on the close interaction of tumour cells and the tumour microenvironment (TME). Although the TME contributes to poor therapy responses and immune evasion, immune cells within the TME can be therapeutically leveraged, as exemplified by immune checkpoint blockade (ICB). Unfortunately, only a small subset of patients with CRC benefit from ICB therapy; those with immune-activated, microsatellite unstable CRC respond, whereas the predominant group of patients with CRC, those with microsatellite-stable tumours, do not. Although challenging, modulating the TME of CRC to convert these lowly immunogenic and immunosuppressed tumours into immune-activated tumours holds tremendous therapeutic potential. In this Review we provide an overview of the cellular and molecular components of immunity in the TME of CRCs at various stages of disease as well as the mechanisms of immunosuppression and immune evasion. We further describe how systemic and local therapies for CRC impact the tumour and systemic immune microenvironments, and how immunity could serve as a therapeutic and prognostic biomarker. Lastly, we highlight novel immunotherapeutic strategies and approaches that modulate the TME of CRCs to make them amenable to immunotherapy.
期刊介绍:
Nature Reviews Cancer, a part of the Nature Reviews portfolio of journals, aims to be the premier source of reviews and commentaries for the scientific communities it serves. The correct abbreviation for abstracting and indexing purposes is Nat. Rev. Cancer. The international standard serial numbers (ISSN) for Nature Reviews Cancer are 1474-175X (print) and 1474-1768 (online). Unlike other journals, Nature Reviews Cancer does not have an external editorial board. Instead, all editorial decisions are made by a team of full-time professional editors who are PhD-level scientists. The journal publishes Research Highlights, Comments, Reviews, and Perspectives relevant to cancer researchers, ensuring that the articles reach the widest possible audience due to their broad scope.