Distinct evolutionary patterns of tumour-immune escape and elimination determined by extracellular matrix architectures.

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.