{"title":"Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer","authors":"Mojdeh Shakiba, David A. Tuveson","doi":"10.1038/s41590-025-02134-6","DOIUrl":null,"url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers that has yet to benefit from immunotherapies. This is primarily a result of its characteristic ‘cold’ tumor microenvironment composed of cancer-associated fibroblasts (CAFs), a dense network of extracellular matrix and several immune cell types, the most abundant of which are the tumor-associated macrophages (TAMs). Advances in single-cell and spatial technologies have elucidated the vast functional heterogeneity of CAFs and TAMs, their symbiotic relationship and their cooperative role in the tumor microenvironment. In this Review, we provide an overview of the heterogeneity of CAFs and TAMs, how they establish an immunosuppressive microenvironment and their collaboration in the remodeling of the extracellular matrix. Finally, we examine why the impact of immunotherapy in PDAC has been limited and how a detailed molecular and spatial understanding of the combined role of CAFs and TAMs is paramount to the design of effective therapies.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"41 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-025-02134-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers that has yet to benefit from immunotherapies. This is primarily a result of its characteristic ‘cold’ tumor microenvironment composed of cancer-associated fibroblasts (CAFs), a dense network of extracellular matrix and several immune cell types, the most abundant of which are the tumor-associated macrophages (TAMs). Advances in single-cell and spatial technologies have elucidated the vast functional heterogeneity of CAFs and TAMs, their symbiotic relationship and their cooperative role in the tumor microenvironment. In this Review, we provide an overview of the heterogeneity of CAFs and TAMs, how they establish an immunosuppressive microenvironment and their collaboration in the remodeling of the extracellular matrix. Finally, we examine why the impact of immunotherapy in PDAC has been limited and how a detailed molecular and spatial understanding of the combined role of CAFs and TAMs is paramount to the design of effective therapies.
期刊介绍：
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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