Authors | Chandler D. Gatenbee, Ann-Marie Baker, Ryan O. Schenck, Margarida Neves, Sara Yakub Hasan, Pierre Martinez, William C.H. Cross, Marnix Jansen, Manuel Rodriguez-Justo, Andrea Sottoriva, Simon Leedham, Mark Robertson-Tessi, Trevor A. Graham and Alexander Anderson |
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Description | Colorectal cancer develops from its precursor lesion, the adenoma. The immune system is hypothesized to be key in modulating progression, but tumor-immune eco-evolutionary dynamics remain uncharacterized. Here, we demonstrate a key role for immune evasion in the progression of human benign disease to colorectal cancer. We constructed a mathematical model of tumor-immune eco-evolutionary dynamics that predicted ecological succession, from an “immune-hot” adenoma immune ecology rich in T cells to an “immune-cold” carcinoma ecology, deficient in T cells and rich in immunosuppressive cells. Using a cross-sectional cohort of adenomas and carcinomas, we validated this prediction by direct measurement of the tumor-immune ecology using whole-slide 10-marker immunohistochemistry (IHC), and analysis of neoantigen clonal architecture multi-region exome sequencing data. Changes in immune ecology relax selection against antigens with high recognition potentials. This study indicates that immune surveillance represents a key evolutionary bottleneck in the evolution of colon cancer. |
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