{"title":"Distinct evolutionary patterns of tumour-immune escape and elimination determined by extracellular matrix architectures.","authors":"Yijia Fan, Jason T George","doi":"10.1098/rsif.2025.0116","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer progression remains a significant clinical challenge. Phenotypic adaptation by tumour cells results in disease heterogeneity, which drives treatment resistance and immune escape. T-cell immunotherapy, while effective at treating some cancer subtypes, can also fail due to limits on tumour immunogenicity or T-cell recognition. For example, one potential contributor to immune escape involves the density and alignment of the extracellular matrix (ECM) surrounding tumours, also known as tumour-associated collagen signature (TACS). However, the specific mechanisms by which aligned fibres contribute to decreased patient survival rates have not yet been decoupled. Here, we developed EVO-ACT (EVOlutionary agent-based cancer T-cell interaction), a two-dimensional agent-based modelling framework designed to investigate how different TACS architectures impact tumour evolution and dynamic interactions with CD8[Formula: see text] T cells. Our results highlight that TACS-driven modulation of T-cell dynamics, combined with phenotypic adaptation, such as epithelial-to-mesenchymal transition, underlies differences in tumour immunogenicity and the application of our model can successfully recapitulate clinically observed breast cancer survival trends.</p>","PeriodicalId":17488,"journal":{"name":"Journal of The Royal Society Interface","volume":"22 228","pages":"20250116"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312568/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of The Royal Society Interface","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1098/rsif.2025.0116","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Cancer progression remains a significant clinical challenge. Phenotypic adaptation by tumour cells results in disease heterogeneity, which drives treatment resistance and immune escape. T-cell immunotherapy, while effective at treating some cancer subtypes, can also fail due to limits on tumour immunogenicity or T-cell recognition. For example, one potential contributor to immune escape involves the density and alignment of the extracellular matrix (ECM) surrounding tumours, also known as tumour-associated collagen signature (TACS). However, the specific mechanisms by which aligned fibres contribute to decreased patient survival rates have not yet been decoupled. Here, we developed EVO-ACT (EVOlutionary agent-based cancer T-cell interaction), a two-dimensional agent-based modelling framework designed to investigate how different TACS architectures impact tumour evolution and dynamic interactions with CD8[Formula: see text] T cells. Our results highlight that TACS-driven modulation of T-cell dynamics, combined with phenotypic adaptation, such as epithelial-to-mesenchymal transition, underlies differences in tumour immunogenicity and the application of our model can successfully recapitulate clinically observed breast cancer survival trends.
期刊介绍:
J. R. Soc. Interface welcomes articles of high quality research at the interface of the physical and life sciences. It provides a high-quality forum to publish rapidly and interact across this boundary in two main ways: J. R. Soc. Interface publishes research applying chemistry, engineering, materials science, mathematics and physics to the biological and medical sciences; it also highlights discoveries in the life sciences of relevance to the physical sciences. Both sides of the interface are considered equally and it is one of the only journals to cover this exciting new territory. J. R. Soc. Interface welcomes contributions on a diverse range of topics, including but not limited to; biocomplexity, bioengineering, bioinformatics, biomaterials, biomechanics, bionanoscience, biophysics, chemical biology, computer science (as applied to the life sciences), medical physics, synthetic biology, systems biology, theoretical biology and tissue engineering.