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bioRxiv · 10.1101/2024.05.13.594017

Distinct evolutionary patterns of tumor immune escape and elimination determined by ECM architectures

Fan, Y.·George, J. T.
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Abstract

Cancer progression remains a significant clinical challenge. Phenotypic adaptation by tumor cells results in disease hetero-geneity, which drives treatment resistance and immune escape. T cell immunotherapy, while effective at treating some cancer subtypes, can also fail due to limits on tumor immunogenicity or T cell recognition. For example, one potential contributor to immune escape involves the density and alignment of the extracellular matrix (ECM) surrounding tumors, also known as Tumor-Associated Collagen Signature (TACS). However, the specific mechanisms by which aligned fibers contribute to decreased patient survival rates have not yet been decoupled. Here, we developed our EVO-ACT (EVOlutionary Agent-based Cancer T cell interaction) model to study how TACS affects tumor evolution and dynamic tumor-T cell interactions. We identified a variety of TACS-specific dynamical features that influence T cell infiltration, cancer immunoediting, and ultimate immune escape. Our model demonstrates how TACS and phenotypic adaptation together explain overall survival trends in breast cancer.

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Fan, Y., George, J. T.. 2024-05-15. Distinct evolutionary patterns of tumor immune escape and elimination determined by ECM architectures. https://doi.org/10.1101/2024.05.13.594017

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